Thanks Lori,
I think this is very helpful as we don't have the time to do this.
Dr. Sharmini V. Rogers, MBBS, MPH, Chief
Bureau of Genetics and Healthy Childhood
Section for Healthy Families and Youth
Division of Community and Public Health
Missouri Department of Health and Senior Services
930 Wildwood Drive
Jefferson City MO 65109
E-mail: [log in to unmask]
Tel: 573-751-6214
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information to the intended recipient, unauthorized disclosure, copying,
distribution or use of the contents of this transmission is strictly
prohibited. If you have received this message in error, please notify
the sender immediately at the following email address
[log in to unmask] . Thank you
>>> "Williamson, Lori L. (HSC)" <[log in to unmask]> 12/6/2007
9:22 AM >>>
Folks,
I don*t know if you*ll appreciate this or want to curse me, but I
was doing a lit search of recent NBS articles (since our meeting in
September) and, in the course of that search, came across articles that
were relevant to NBS, genetics, public health, hearing NBS, and
hemoglobinopathy NBS. The lit search is basically the last 6 months,
English, mostly US experiences. If it is bothersome to receive this
type of email, I won*t do it again. I*m just testing the waters as
to whether or not this is valuable. If it is valuable, but you don*t
want it in your email, maybe we could do web postings. Just let me
know.
1: Hemoglobin. 2007;31(2):129-34.
Three new beta-globin gene promoter mutations identified through
newborn
screening.
Eng B, Walker L, Nakamura LM, Hoppe C, Azimi M, Lee H, Waye JS.
Hamilton Regional Laboratory Medicine Program, Hamilton Health
Sciences,
Hamilton, Ontario, Canada.
We report three new beta-globin gene promoter mutations identified in
newborns
with hemoglobin (Hb) profiles consistent with Hb S/beta(+)-thalassemia
(thal)
(Hbs FSA). All three mutations are in close proximity to the conserved
ATAA
sequence located at positions -31 to -28 relative to the mRNA Cap site.
Two cases
involved single base substitutions at positions -25 (G-->C) and -32
(C-->T). The
remaining case involved the deletion of two bases (-AA) at positions
-27 and -26.
Publication Types:
Case Reports
PMID: 17486493 [PubMed - indexed for MEDLINE]
2: Clin Genet. 2007 May;71(5):446-50.
Newborn screening for mucopolysaccharidoses: opinions of patients and
their
families.
Hayes IM, Collins V, Sahhar M, Wraith JE, Delatycki MB.
The Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens
Research
Institute, Royal Children's Hospital, Parkville, Victoria, Australia.
We have conducted a study to assess the opinions of parents of
individuals with
mucopolysaccharidoses (MPS) and adults with MPS regarding newborn
screening (NBS)
for this condition, as testing is now technically possible. A
questionnaire
including a number of hypothetical clinical scenarios about NBS for MPS
was
distributed to members of MPS support groups from United States and
Australia.
Questionnaires were returned by 249 members of the US (40% response)
and
Australian (38% response) support groups. Eleven respondents were
adults with MPS
and the rest were parents of individuals with MPS. Eighty-six percent
of
respondents indicated that they would have wanted NBS for their own
children.
Ninety-seven percent supported the use of NBS for MPS in situations
where early
treatment that favorably impacts on disease outcome is available, 87%
supported
NBS when a severe form of MPS was diagnosed, but no treatment is
available that
improves the long-term outcome and 84% supported NBS for mild MPS where
no
disease-modifying treatment is available. The most common reason cited
in support
of NBS was that NBS could avoid a delay in diagnosis and the
accompanying
distress that delayed diagnosis created. This study has identified
strong support
for the introduction of NBS for MPS from this group. Psychosocial
benefits of
screening may outweigh potential harms.
PMID: 17489850 [PubMed - indexed for MEDLINE]
3: Minn Med. 2007 May;90(5):33-5.
Genetic tests physicians should know.
Mensink K, Ferber M.
Molecular Genetics Laboratory and Multidisciplinary Neurofibromatosis
Clinic,
USA.
Seven years after completion of the human genome draft sequence,
significant
advances have been made in genetic testing. This article highlights
some of the
newest and most important genetic diagnostic and screening tests to
come to
market in recent years. Application of these tests to clinical practice
is also
discussed.
PMID: 17550084 [PubMed - indexed for MEDLINE]
4: J Pediatr Endocrinol Metab. 2007 Apr;20(4):457-8.
"The Newborn Screening Saves Lives Act"--four million calls for
support!
Rivkees SA.
Publication Types:
Editorial
PMID: 17550207 [PubMed - indexed for MEDLINE]
5: Am J Audiol. 2007 Jun;16(1):29-56.
Evaluating families' satisfaction with early hearing detection and
intervention
services in Massachusetts.
MacNeil JR, Liu CL, Stone S, Farrell J.
Massachusetts Department of Public Health, Boston, MA 02108, USA.
[log in to unmask]
PURPOSE: To determine levels of families' satisfaction and anxiety
associated
with the early hearing detection and intervention (EHDI) process in
Massachusetts, and to assess the relationship between a child's hearing
status
and levels of family satisfaction. METHOD: Surveys were mailed to
families whose
infants (a) passed their initial hearing screening (Group 1), (b) did
not pass
their initial screening but subsequently passed an outpatient rescreen
or
diagnostic evaluation (Group 2), or (c) were identified with permanent
hearing
loss (Group 3). Survey instruments measured families' satisfaction and
anxiety
associated with each stage of the EHDI process. RESULTS: Of the 4,138
families
surveyed, 1,106 (27%) responded. Families reported satisfaction with
screening
services (Group 1 = 88%; Group 2 = 86%; Group 3 = 75%), and few
reported anxiety
prior to the hearing screening (Group 1= 4%; Group 2 = 15%; Group 3 =
19%). Among
families requiring retesting services, 97% of Group 2 and 87% of Group
3 families
were satisfied. Among Group 3 families, 94% reported satisfaction with
the care
their audiologist was providing, and 79% were satisfied with their
early
intervention services overall. CONCLUSIONS: Families reported
satisfaction with
the EHDI services they received in Massachusetts and expressed strong
support for
the universal newborn hearing screening initiative.
Publication Types:
Evaluation Studies
Research Support, U.S. Gov't, P.H.S.
PMID: 17562754 [PubMed - indexed for MEDLINE]
6: Clin Chem. 2007 Aug;53(8):1401-7. Epub 2007 Jun 22.
Assessing quality and functionality of DNA from fresh and archival
dried blood
spots and recommendations for quality control guidelines.
Sjöholm MI, Dillner J, Carlson J.
The Swedish National Biobanking Program, Lund University, Malmö
University
Hospital, Malmö, Sweden.
BACKGROUND: Dried blood spots (DBS) are a convenient and inexpensive
method for
biobanking. Although many countries have established population-based
DBS
biobanks from neonatal screening programs, the quality and usefulness
of DNA from
DBS have not been extensively assessed. METHODS: We compared 4 common
DNA
extraction methods (Qiagen, EZNA, Chelex 100, and alkaline lysis) in a
pilot
study using fresh DBS with known lymphocyte count. We assessed
suitability for
multiple displacement amplification (MDA) and subsequent
single-nucleotide
polymorphism (SNP) analyses. We selected the EZNA method for DNA
extraction from
archival samples up to 27 years old, stored at room temperature or -20
degrees C,
and SNP analyses were performed after MDA. RESULTS: Extraction using
alkaline
lysis failed in most tests, and Chelex 100 was unsuccessful in
real-time PCR,
whereas the EZNA and Qiagen methods were successful by all evaluated
quality
indices. DNA extraction by EZNA, MDA, and SNP analyses were successful
for the
archival samples stored at -20 degrees C. CONCLUSION: Routine protocols
for
evaluation of the quality and functional integrity of DNA based on DNA
yield, DNA
size, and quantification of amplifiable DNA allow use of sufficient
template for
MDA and successful SNP analyses from both primary DBS extract and MDA
product. A
single 3-mm disc can yield sufficient DNA for several thousand SNP
analyses. DNA
from DBS is thus suitable for genetic epidemiology studies.
Publication Types:
Comparative Study
Research Support, Non-U.S. Gov't
PMID: 17586590 [PubMed - indexed for MEDLINE]
7: Clin Genet. 2007 Jul;72(1):39-46.
Does cystic fibrosis neonatal screening detect atypical CF forms?
Extended
genetic characterization and 4-year clinical follow-up.
Narzi L, Ferraguti G, Stamato A, Narzi F, Valentini SB, Lelli A,
Delaroche I,
Lucarelli M, Strom R, Quattrucci S.
Department of Paediatrics, Cystic Fibrosis Centre, University of Rome
La
Sapienza, Rome, Italy.
The neonatal screening protocol for cystic fibrosis (CF) is based on a
first
determination of blood immunoreactive trypsin (IRT1), followed by a
first level
genetic test that includes the 31 worldwide most common mutations of
the cystic
fibrosis transmembrane conductance regulator (CFTR) gene (DNA31), and a
second
determination of blood immunoreactive trypsin (IRT2). This approach
identifies,
in addition to affected subjects, a high proportion of newborns with
hypertrypsinaemia at birth, in whom only one mutation is identified and
who have
a negative or borderline sweat test and pancreatic sufficiency.
Although it has
been suggested that hypertrypsinaemia may be caused by a single CFTR
mutation,
whether such neonates should be merely considered as healthy carriers
remains a
matter of debate as hypertrypsinaemia at birth may be a biochemical
marker of a
CFTR malfunction because of a second mild mutation. We analyzed, by
means of an
extended sequencing protocol, 32 newborns who tested positive at an
IRT1/DNA31/IRT2 screening protocol and in whom only one CFTR mutation
was found.
The results obtained demonstrate that 62.5% of these newborns were also
carrying
a second mild CFTR mutation. The high proportion of compound
heterozygous
subjects, combined with the results of a 4-year follow-up in nine of
these
subjects all of whom displaying initial CF clinical symptoms, suggest
that it may
be possible to use the IRT1/DNA31/IRT2 protocol of neonatal screening
to identify
newborns with atypical forms of CF. In view of these findings, an
extended
genetic search for subjects with compound heterozygosity and a periodic
clinical
assessment should be considered.
Publication Types:
Research Support, Non-U.S. Gov't
PMID: 17594398 [PubMed - indexed for MEDLINE]
8: J Inherit Metab Dis. 2007 Oct;30(5):812. Epub 2007 Jun 21.
The tetrahydrobiopterin loading test in 36 patients with
hyperphenylalaninaemia:
evaluation of response and subsequent treatment.
Bóveda MD, Couce ML, Castiñeiras DE, Cocho JA, Pérez B, Ugarte M, Fraga
JM.
Laboratorio Metabolopatías, Hospital Clínico Universitario, Planta 0,
Trav.
Choupana s/n, 15706, Santiago de Compostela, Spain.
[log in to unmask]
The response to tetrahydrobiopterin (BH4) in patients with
phenylalanine
hydroxylase (PAH, EC 1.14.16.1) deficiency (OMIM 261600) has been
widely
reported. Here we report results of the BH4 loading test (20 mg/kg per
day) in a
group of 36 patients with PAH deficiency and phenotype of mild
hyperphenylalaninaemia (HPA), mild phenylketonuria (PKU) or classic
PKU. The
patients ranged from neonates aged 7-15 days, detected in the Newborn
Screening
Programme for PKU in the population of Galicia (NW Spain), to adults
aged up to
32 years who had been receiving a low-phenylalanine (Phe) diet for a
period of
years. Ten of the 36 patients showed a reduction of more than 30% in
plasma Phe
levels within 24 h of BH4 loading (ranging from 33.7% to 90.2%, mean
59.2%, SD
19.8%). All the patients with mild HPA (100%) showed a positive
response; 57% of
patients with mild PKU (4 of 7) showed a positive response. Of
particular
interest were positive responses in two patients with classic PKU, and
in one
patient with mutations of the phenylalanine hydroxylase (PAH) gene that
have not
to date been reported to be BH4-responsive (p.S303A and p.G46S). BH4
treatment
(5-8 mg/kg per day) was commenced in 9 of the 10 BH4-responsive
patients. The
observed responses to treatment argue for application of the BH4
loading test in
all patients with HPA or PKU, independently of genotype, phenotype or
age.
PMID: 17603758 [PubMed - indexed for MEDLINE]
9: J Med Screen. 2007;14(2):55-9.
Prevalence of neural tube defect pregnancies in England and Wales from
1964 to
2004.
Morris JK, Wald NJ.
Wolfson Institute of Preventive Medicine, Barts and the London Queen
Mary's
School of Medicine and Dentistry, Charterhouse Square, London EC1M 6BQ,
UK.
[log in to unmask]
OBJECTIVES: To determine the prevalence of pregnancies with a neural
tube defect
(NTD) in England and Wales between 1964 and 2004 and to estimate the
relative
impact of antenatal screening and a change in the incidence of these
defects on
the prevalence of births with NTDs. SETTINGS: Use of data published by
the Office
for National Statistics (ONS) on terminations of pregnancies with an
NTD and
births with an NTD from 1964 to 2004. METHODS: Estimates were made of
the total
number of terminations of pregnancies and births with an NTD by taking
account of
the under-reporting of these terminations and births using a previously
described
method. In 1995 ONS started to report the number of terminations with
an NTD
rather than the total numbers of terminations with a central nervous
system (CNS)
malformation that had previously been used to estimate the number of
NTD
terminations. Adjustment was made for this and new estimates of the
total number
of NTD pregnancies were produced to 2004. RESULTS: There were an
estimated 969
pregnancies with NTDs (168 (17%) births and 801(83%) terminations) in
England and
Wales in 2004. An estimated 44% of NTD terminations and 32% of births
were not
reported as such. The birth prevalence per 1000 decreased fallen 93%
from 3.6 in
1964 to 0.3 in 2004, 59% due to an underlying decrease in the
prevalence of NTDs
and 34% due to screening diagnosis and subsequent termination of
affected
pregnancies. CONCLUSION: The prevalence of NTD pregnancies decreased by
around
two per 1000 from 1964 to 1990 and thereafter remained fairly constant.
The
prevalence of NTD pregnancies is substantially underestimated if it is
based only
on reported NTD births (by 88%) and also if it is based on reported NTD
births
and terminations (by 52%), because most NTD pregnancies in England and
Wales are
terminated following antenatal screening and most of these terminations
are not
reported.
PMID: 17626701 [PubMed - indexed for MEDLINE]
10: J Womens Health (Larchmt). 2007 Jun;16(5):575-82.
Sickle cell disease: current activities, public health implications,
and future
directions.
Creary M, Williamson D, Kulkarni R.
Division of Blood Disorders, National Center on Birth Defects and
Developmental
Disabilities, Centers for Disease Control and Prevention, Atlanta,
Georgia 30333,
USA. [log in to unmask]
Sickle cell disease (SCD) is a genetic blood disorder caused by
abnormal
hemoglobin that damages and deforms red blood cells (RBCs). The
abnormal red
cells break down, causing anemia, and obstruct blood vessels, leading
to
recurrent episodes of severe pain and multiorgan ischemic damage. SCD
affects
millions of people throughout the world and is particularly common
among people
whose ancestors come from sub-Saharan Africa. Sickle cell trait (SCT)
is an
inherited condition in which both normal hemoglobin and sickle
hemoglobin are
produced in the RBCs. SCT is not a type of sickle cell disease. People
with SCT
are generally healthy. In SCD, clinical severity varies, ranging from
mild and
sometimes asymptomatic states to severe symptoms requiring
hospitalization.
Symptomatic treatments exist, but there is no cure for SCD. Although
there has
been extensive clinical and basic science research in SCD, many public
health
issues, such as blood safety surveillance, compliance with
immunizations,
follow-up of newborns with positive screening tests, stroke prevention,
pregnancy
complications, pain prevention, quality of life, and thrombosis, in
people with
SCT remain unaddressed. Currently, efforts are under way to strengthen
SCD-related activities within the Centers for Disease Control and
Prevention
(CDC). To date, several activities are being or have been conducted by
centers
within CDC, including quality assurance of newborn screening tests for
SCD,
morbidity and mortality studies, genetic studies, and studies focusing
on the
protective effects of SCT for malaria. This paper discusses the public
health
implications of SCD, summarizes SCD-related activities within CDC, and
points to
future directions that the agency can take to begin to address some of
these
issues.
Publication Types:
Review
PMID: 17627395 [PubMed - indexed for MEDLINE]
11: J Inherit Metab Dis. 2007 Aug;30(4):613. Epub 2007 Jul 12.
Neonatal screening of cystic fibrosis: diagnostic problems with CFTR
mild
mutations.
Roussey M, Le Bihannic A, Scotet V, Audrezet MP, Blayau M, Dagorne M,
David V,
Deneuville E, Giniès JL, Laurans M, Moisan-Petit V, Rault G, Vigneron
P, Férec C.
Centre de Ressources et de compétences de la mucoviscidose, Université
de Rennes
1 et Association Régionale de Dépistage et de Prévention des Handicaps
de
l'Enfant de Bretagne, Rennes, France. [log in to unmask]
Newborn screening (NBS) of cystic fibrosis (CF) was implemented
throughout the
whole of France in 2002, but it had been established earlier in three
western
French regions. It can reveal atypical CF with one or two known CFTR
mild
mutations, with an uncertain evolution. The sweat test can be normal
or
borderline. In Brittany, from 1989 to 2004, 196 CF cases were diagnosed
(1/2885
births). The incidence of atypical CF diagnosed by NBS is 9.7% (19 from
196). The
outcome of 17 (2 lost of view) has been studied, with 9 other atypical
CF cases
diagnosed by NBS in two other regions. The follow-up period extends
from 0.25 to
19.8 years (NBS implemented in Normandy in 1980) with mean age 4.6
years. The
most frequent mild mutation is R117H ISV8-7T (50%). At the time of the
last
visit, nutritional status is normal. All these CF patients are
pancreatic
sufficient. Only one patient exhibits respiratory infections, whereas 7
others
have them intermittently. Two of them had intermittent Pseudomonas
aeruginosa
colonization at 2.8 and 6.5 years. Mean Shwachman score is 96.7, mean
Brasfield
score is 22.8. Eight children have had lung function tests (mean
follow-up of 10
years): mean FVC was 99% of predicted, mean FEV1 101%, but one of them
has FEV1
of 48%. Predicting the phenotype of these atypical CF patients remains
difficult,
thus complicating any genetic counselling. A regular clinical
evaluation is
necessary, if possible by a CF unit, because CF symptoms may appear
later.
PMID: 17632692 [PubMed - indexed for MEDLINE]
12: J Inherit Metab Dis. 2007 Aug;30(4):585-92. Epub 2007 Jul 23.
Reduction of the false-positive rate in newborn screening by
implementation of
MS/MS-based second-tier tests: the Mayo Clinic experience (2004-2007).
Matern D, Tortorelli S, Oglesbee D, Gavrilov D, Rinaldo P.
Biochemical Genetics Laboratory, Mayo Clinic College of Medicine,
Rochester,
Minnesota 55905, USA. [log in to unmask]
The continued expansion of newborn screening programmes to include
additional
conditions increases the responsibility of newborn screening
laboratories to
provide testing with the highest sensitivity and specificity to allow
for
identification of affected patients while minimizing the false-positive
rate.
Some assays and analytes are particularly problematic. Over recent
years, our
laboratory tried to improve this situation by developing second-tier
tests to
reduce false-positive results in the screening for congenital adrenal
hyperplasia
(CAH), tyrosinaemia type I, methylmalonic acidaemias, homocystinuria,
and maple
syrup urine disease (MSUD). Beginning in 2004, this approach was
applied to
Mayo's newborn screening programme and resulted in a false-positive
rate of
0.09%, a positive predictive value of 41%, and a positive detection
rate of 1
affected case in 1672 babies screened.
PMID: 17643193 [PubMed - indexed for MEDLINE]
13: J Inherit Metab Dis. 2007 Aug;30(4):447-65. Epub 2007 Jul 23.
Newborn screening in North America.
Therrell BL, Adams J.
Department of Pediatrics, University of Texas Health Science Center at
San
Antonio, San Antonio, TX, USA. [log in to unmask]
Newborn screening in North America dates to the early work of Bob
Guthrie in the
USA. Screening programmes in both the USA and Canada began in the early
1960s,
with documented programmes in both countries as early as 1962.
Throughout the
1960s and 1970s, many of the screening tests that later became part of
routine
screening around the world were developed in US and Canadian
laboratories,
including tests for phenylketonuria, other inborn errors of
metabolism,
congenital hypothyroidism, congenital adrenal hyperplasia, and
haemoglobinopathies. An automated punching machine developed in the
USA
facilitated screening expansion by significantly reducing sample
preparation time
and effort. US and Canadian programmes were leaders in applying
computerized data
management to newborn screening in the 1980s. In the 1990s, DNA and
tandem mass
spectrometry testing protocols were developed in the USA and applied to
newborn
screening. US programmes have continually expanded over time, while
most Canadian
programmes have not. With impetus from private laboratories and
professional and
consumer groups, many US programmes now screen for more than 50
conditions and
there is increased expansion activity in Canada. NBS research in the
USA is
focused on improving system efficiency and translating other genetic
testing to
NBS, particularly where new technologies and treatment therapies exist.
Although
national newborn screening policies do not exist in either Canada or
the USA,
there are intense efforts to provide uniform access to screening
nationwide in
both countries. New partnerships between health professionals,
consumers and
politicians are benefiting the overall screening systems in both
countries.
Publication Types:
Historical Article
PMID: 17643194 [PubMed - indexed for MEDLINE]
14: Circulation. 2007 Jul 24;116(4):e92; author reply e93.
Comment on:
Circulation. 2007 Jan 23;115(3):294-6. Circulation. 2007 Jan
23;115(3):361-7. Circulation. 2007 Jan 23;115(3):368-76.
Letter by O'Rourke regarding articles, "Prevalence of long-QT syndrome
gene
variants in sudden infant death syndrome," "Cardiac sodium channel
dysfunction in
sudden infant death syndrome," and "Contribution of long-QT syndrome
genes to
sudden infant death syndrome: is it time to consider newborn
electrocardiographic
screening?".
O'Rourke MF.
Publication Types:
Comment
Letter
PMID: 17646591 [PubMed - indexed for MEDLINE]
15: Pediatr Pulmonol. 2007 Sep;42(9):773-8.
A sweat test centered protocol for the disclosure and diagnosis of
cystic
fibrosis in a newborn screening program.
Doull IJ, Hall SJ, Bradley DM.
Respiratory/Cystic Fibrosis Unit, Children's Hospital for Wales,
Cardiff, Wales,
United Kingdom. [log in to unmask]
We describe the development of a sweat test centered protocol for
disclosure and
diagnosis of Cystic Fibrosis. Our protocol aims to identify infants
early,
minimizes the time of uncertainty for the parents, and yet gives them
time to
begin to come to terms with the possibility of diagnosis. Over a 9-year
period
295,247 newborn infants were screened for CF in Wales, of whom 121
infants were
diagnosed as having CF. During this period there were four false
negatives
(3.3%). Parental satisfaction with the process appears very high 6
months after
disclosure. (c) 2007 Wiley-Liss, Inc.
PMID: 17659601 [PubMed - in process]
16: Eur J Pediatr. 2007 Jul 28 [Epub ahead of print]
Outcome of three cases of untreated maternal glutaric aciduria type I.
Garcia P, Martins E, Diogo L, Rocha H, Marcão A, Gaspar E, Almeida M,
Vaz C,
Soares I, Barbot C, Vilarinho L.
Hospital Pediátrico de Coimbra, Av. Bissaya Barreto, 3000, Coimbra,
Portugal.
We report, for the first time, the outcome of three children born to
two women
with untreated glutaric aciduria type I (GA I). Isolated
hypocarnitinemia in
neonatal screening in one baby allowed the identification of the
disease in his
mother, who was undiagnosed so far and had had a previous daughter. The
other
baby was born to an already diagnosed mother who was not treated;
newborn
screening in the child reflected the metabolic state of the mother.
Biochemical
abnormalities returned to normal within one week. At the age of 4
months,
neuroimaging showed Sylvian enlargement in both infants and bilateral
temporal
arachnoid cysts in one. Physical and neurological developments were
normal for
the three patients at ages 2 and 5 years. We conclude that long-term
follow up
will determine the true impact of GA I in such children.
PMID: 17661081 [PubMed - as supplied by publisher]
17: Health Commun. 2007;22(2):115-21.
Attributions and reported communication of a diagnosis of down
syndrome.
Elwy AR, Michie S, Marteau TM.
Center for Health Quality, Outcomes and Economic Research, Edith Nourse
Rogers
Memorial Hospital, Veterans Health Administration, Department of
Veterans
Affairs, Boston University School of Public Health, Boston,
Massachusetts, USA.
[log in to unmask]
This study investigates attributions and reported communication in 97
neonatologists who responded to a vignette-based questionnaire
depicting a woman
with 1 of 3 prenatal screening histories for Down syndrome (DS) who had
just
given birth to a child with DS: not offered screening, refused
screening, or
received a false negative result on screening. Neonatologists reported
blaming
and attributing more control to women who refused prenatal screening
for DS.
Attributions of blame, but not control, were associated with reports
of
communicating more negative information on DS to parents.
Neonatologists may make
attributions about women on the basis of their screening histories,
which appear
to influence some but not all aspects of how they report communicating
a
diagnosis of DS.
Publication Types:
Randomized Controlled Trial
PMID: 17668991 [PubMed - indexed for MEDLINE]
18: J Inherit Metab Dis. 2007 Aug;30(4):556-62. Epub 2007 Aug 6.
Effects and clinical significance of tetrahydrobiopterin
supplementation in
phenylalanine hydroxylase-deficient hyperphenylalaninaemia.
Gramer G, Burgard P, Garbade SF, Lindner M.
Zentrum für Kinder- und Jugendmedizin, Heidelberg, Germany.
In recent years several studies on tetrahydrobiopterin
(BH4)-responsive
phenylalanine hydroxylase (PAH) deficiency have been published. The
molecular
mechanisms of BH4 responsiveness are not conclusively understood, but
there is
evidence that BH4 responsiveness in hyperphenylalaninaemia (HPA)
depends on the
patient's genotype and residual PAH activity. As a BH4 preparation will
soon
obtain marketing approval as an alternative treatment for
phenylketonuria (PKU),
it is particularly important to evaluate this treatment and to define
criteria to
identify patients with a potential benefit from it. Most of the
patients found to
be BH4-responsive suffered from mild PKU or mild hyperphenylalaninaemia
(MHP) and
some of these would not be treated at all in many countries. Of
patients with
moderate and classic forms of PKU, only a few were classified as
responders and
the clinical significance of the effect size may be small.
PMID: 17680344 [PubMed - indexed for MEDLINE]
19: J Inherit Metab Dis. 2007 Aug;30(4):600-5. Epub 2007 Aug 10.
Structures for clinical follow-up: newborn screening.
Howell RR, Engelson G.
Department of Pediatrics, Miller School of Medicine, University of
Miami, P.O.
Box o16820, Miami, FL 33101, USA. [log in to unmask]
Clinical follow-up of children identified by newborn screening is
critical in
ensuring that the short-term and long-term needs of the newborn infant
are
managed. Within the United States, one of the biggest challenges in the
newborn
screening programme is clinical follow-up, and there still remains wide
variation
in practice patterns among states on how infants are followed up. In
addition,
there is lack of consistency in the treatment and diagnostic protocols
used by
health care providers. There is growing interest in the establishment
of a
systematic process for follow-up and for the development of a
nationwide
infrastructure that will ensure that all children will be provided
consistent and
effective treatment in a timely manner. Within this framework of
optimal
diagnosis and therapy, there must also be opportunities to study the
natural
history of these conditions, to monitor short- and long-term health
outcomes, to
assist with policy decision-making, to validate the effectiveness of
screening,
to define the clinical spectrum of the diseases, and to provide
opportunities for
the advancement of novel therapeutic interventions and
screening/diagnostic
technologies. It will only be through the development of a structured
clinical
follow-up system that we will be able to make certain these newborn
infants are
provided the most appropriate treatment for their disease variants and
allow
researchers to make more rapid advances in improving the clinical
management of
these conditions.
PMID: 17694355 [PubMed - indexed for MEDLINE]
20: Genet Med. 2007 Aug;9(8):518-27.
Assuring clinical genetic services for newborns identified through U.S.
newborn
screening programs.
Kaye CI, Livingston J, Canfield MA, Mann MY, Lloyd-Puryear MA, Therrell
BL Jr.
Office of Education, University of Colorado School of Medicine, Denver,
Colorado,
USA.
PURPOSE: The study purpose was to determine whether U.S. newborn
screening and/or
genetics programs systematically document whether newborns and their
families,
identified with genetic disorders through newborn dried blood spot
screening,
receive clinical genetic services. METHODS: Nineteen state genetic
plans were
reviewed and a 30-question survey was administered to 53 respondents,
including
state newborn screening program coordinators and state genetics
program
coordinators in 36 states and principal investigators of 5 Health
Resources and
Services Administration-designated regional genetic and newborn
screening
collaboratives. RESULTS: Survey findings indicate that none of the
state newborn
screening and/or state genetics programs routinely tracked
patient-level data on
clinical genetic services for newborns identified with all of the
genetic and
congenital conditions for which their programs screened. Few programs
could
provide information systematically on whether patients were referred
for, or
received, genetic counseling. CONCLUSIONS: Systematic tracking of
clinical
genetic services for newborns identified by newborn screening programs
is
desirable and manageable. Recent national guidelines recommend tracking
genetic
counseling in newborn screening follow-up. The communications processes
that
state programs currently use to obtain follow-up reports from
subspecialists
could be augmented with clinical genetic service questions. Programs
should be
encouraged and supported in the efforts to track genetic services for
the benefit
of newborns and their families.
Publication Types:
Comparative Study
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
PMID: 17700390 [PubMed - in process]
21: J Inherit Metab Dis. 2007 Aug;30(4):576-84. Epub 2007 Aug 14.
Quality performance of newborn screening systems: strategies for
improvement.
Webster D.
NZ National Testing Centre, PO Box 872, Auckland, New Zealand.
[log in to unmask]
Newborn metabolic screening is a public health activity with the
potential to
realize significant health gains for infants affected with a range of
congenital
conditions. Many of these are inborn errors of metabolism. The
activities
required to achieve the gains are diverse and carried out by a number
of
organizations, by families and by many health care professionals.
Laboratories
have the best-developed quality strategies, which include quality
assurance
programmes, guidelines, protocols and standards. Two-tier testing and
use of
multiple markers improve sensitivity and specificity. There are
international
initiatives to harmonize assay materials and definitions to allow
better
benchmarking between programmes. Outside the laboratory, standards,
education and
protocols improve the quality of specimen collection, diagnosis and
treatment,
which together produce the health gains.
PMID: 17701286 [PubMed - indexed for MEDLINE]
22: Genet Couns. 2007;18(2):209-15.
Associated malformations in cases with neural tube defects.
Stoll C, Alembik Y, Dott B.
Génétique Médicale, Faculté de Médecine, Strasbourg, France.
[log in to unmask]
Infants with neural tube defects (NTDs) may have other associated
congenital
defects. The reported incidence and the types of associated
malformations vary
between different studies. The purpose of this investigation was to
assess the
prevalence of associated malformations in a geographically defined
population.
The prevalences at birth of associated malformations in infants with
NTDs were
collected between 1979 and 2003 on all infants born in the area covered
by the
registry of congenital anomalies of Northeastern France in 334,262
consecutive
births. Of the 360 infants with NTDs born during this period, 20.5 %
had
associated malformations. Associated malformations were more frequent
in infants
who had encephalocele (37.5 %) than in infants with anencephaly (11.8
%) or
infants with spina bifida (23.7 %). Malformations in the face (oral
clefts), in
the musculoskeletal system, in the renal system, and in the
cardiovascular system
were the most common other anomalies. In conclusion the overall
prevalence of
malformations, which was one in five infants, emphasizes the need for a
thorough
investigation of infants with NTDs. A routine screening for other
malformations
especially facial clefts, musculoskeletal, renal and cardiac anomalies
may need
to be considered in infants with NTDs, and genetic counseling seems
warranted in
most of these complicated cases.
PMID: 17710873 [PubMed - indexed for MEDLINE]
23: Birth. 2007 Sep;34(3):238-44.
Information and informed consent for neonatal screening: opinions and
preferences
of parents.
Detmar S, Hosli E, Dijkstra N, Nijsingh N, Rijnders M, Verweij M.
TNO Quality of Life: Prevention and Healthcare, Leiden, The
Netherlands.
BACKGROUND: The current neonatal screening program ("the heel prick")
involves
taking a few drops of blood from almost every newborn in the
Netherlands to
determine whether the child is suffering from one of three congenital
disorders:
phenylketonuria, congenital hypothyroid, or adrenogenital syndrome.
This study
investigated the preferences and views of parents and future parents
with respect
to information about, and consent to, neonatal screening and the
possible
expansion of the program. METHODS: Seven focus group discussions took
place with
future parents, parents with a healthy child, and parents with children
affected
by disorders for which screening is possible, now or in the future
(total of 36
participants). The discussions were audiotaped, transcribed, and
analyzed for
content. RESULTS: Parents were not well informed about what the heel
prick
involves at present. Nevertheless, they see it as a routine procedure
and do not
think about the possibility of refusing it. If the heel-prick program
were to be
expanded, parents would like to be informed earlier, preferably during
pregnancy.
In addition, most parents preferred an opt-out consent approach.
CONCLUSIONS: If
the neonatal screening program is to be expanded, parents would prefer
for
information about the program be given during pregnancy. In addition,
they
preferred an opt-out consent approach, on condition that screening was
for the
purpose of preventing irreversible harm. Parental opinion was divided
on this
issue if the aim of screening were to be widened.
PMID: 17718874 [PubMed - indexed for MEDLINE]
24: J Child Neurol. 2007 Aug;22(8):1019-26.
Spinal muscular atrophy genetic counseling access and genetic
knowledge: parents'
perspectives.
Meldrum C, Scott C, Swoboda KJ.
University of Utah School of Medicine, Salt Lake City, Utah 84132,
USA.
Spinal muscular atrophy is characterized by degeneration of alpha motor
neurons
in the anterior horns of the spinal cord, which leads to progressive
symmetrical
muscle weakness and atrophy. Spinal muscular atrophy is the leading
fatal
autosomal recessive disorder in infancy, and genetic counseling is an
essential
component of the care of families of these patients. However, little
guidance is
available in the published literature regarding the process and benefit
of
genetic counseling for families. Accordingly, the authors designed a
questionnaire to assess parents' knowledge of the disease, gauge their
access to
genetic counseling, and determine how parents use information gained
from
counseling to guide choices for future pregnancies. The questionnaire
specifically targeted when genetic counseling was received, from whom,
parental
knowledge regarding spinal muscular atrophy genetics, parental choices
regarding
spinal muscular atrophy and their child, frequency of prenatal testing,
perceived
relevance of newborn screening, and opinions regarding the disease.
Most families
clearly received some type of genetic counseling. Yet how and from whom
they
received the information varied greatly, as did their genetic knowledge
of spinal
muscular atrophy. The highest percentage of families received
counseling from
neurologists, who may not be appropriately prepared to provide formal
genetic
counseling. Many respondents reported having a negative experience with
genetic
counseling, possibly because it occurred at the time of diagnosis or
shortly
afterward, a period of great emotional turmoil. These data suggest that
a
consistent approach for facilitating how and when genetic counseling is
received
is greatly needed.
Publication Types:
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
PMID: 17761658 [PubMed - indexed for MEDLINE]
25: Pediatrics. 2007 Sep;120(3):481-8.
Improving newborn preventive services at the birth hospitalization: a
collaborative, hospital-based quality-improvement project.
Mercier CE, Barry SE, Paul K, Delaney TV, Horbar JD, Wasserman RC,
Berry P, Shaw
JS.
Department of Pediatrics, University of Vermont, Burlington, Vermont,
USA.
[log in to unmask]
OBJECTIVE: The goal was to test the effectiveness of a statewide,
collaborative,
hospital-based quality-improvement project targeting preventive
services
delivered to healthy newborns during the birth hospitalization.
METHODS: All
Vermont hospitals with obstetric services participated. The
quality-improvement
collaborative (intervention) was based on the Breakthrough Series
Collaborative
model. Targeted preventive services included hepatitis B immunization;
assessment
of breastfeeding; assessment of risk of hyperbilirubinemia; performance
of
metabolic and hearing screens; assessment of and counseling on tobacco
smoke
exposure, infant sleep position, car safety seat fit, and exposure to
domestic
violence; and planning for outpatient follow-up care. The effect of
the
intervention was assessed at the end of an 18-month period.
Preintervention and
postintervention chart audits were conducted by using a random sample
of 30
newborn medical charts per audit for each participating hospital.
RESULTS:
Documented rates of assessment improved for breastfeeding adequacy (49%
vs 81%),
risk for hyperbilirubinemia (14% vs 23%), infant sleep position (13% vs
56%), and
car safety seat fit (42% vs 71%). Documented rates of counseling
improved for
tobacco smoke exposure (23% vs 53%) and car safety seat fit (38% vs
75%).
Performance of hearing screens also improved (74% vs 97%). No
significant changes
were noted in performance of hepatitis B immunization (45% vs 30%) or
metabolic
screens (98% vs 98%), assessment of tobacco smoke exposure (53% vs
67%),
counseling on sleep position (46% vs 68%), assessment of exposure to
domestic
violence (27% vs 36%), or planning for outpatient follow-up care (80%
vs 71%).
All hospitals demonstrated preintervention versus postintervention
improvement of
> or = 20% in > or = 1 newborn preventive service. CONCLUSIONS: A
statewide,
hospital-based quality-improvement project targeting hospital staff
members and
community physicians was effective in improving documented newborn
preventive
services during the birth hospitalization.
Publication Types:
Multicenter Study
PMID: 17766519 [PubMed - indexed for MEDLINE]
26: Ear Hear. 2007 Sep;28(5):605-27.
Vocalizations of infants with hearing loss compared with infants with
normal
hearing: Part I--phonetic development.
Moeller MP, Hoover B, Putman C, Arbataitis K, Bohnenkamp G, Peterson B,
Wood S,
Lewis D, Pittman A, Stelmachowicz P.
Boys Town National Research Hospital, Omaha, Nebraska 68131, USA.
[log in to unmask]
OBJECTIVE: Infants with hearing loss are known to be slower to develop
spoken
vocabulary than peers with normal hearing. Previous research
demonstrates that
they differ from normal-hearing children in several aspects of
prelinguistic
vocal development. Less is known about the vocalizations of
early-identified
infants with access to current hearing technologies. This longitudinal
study
documents changes in prelinguistic vocalizations in early-identified
infants with
varying degrees of hearing loss, compared with a group of infants with
normal
hearing. It was hypothesized that infants with hearing loss would
demonstrate
phonetic delays and that selected aspects of phonetic learning may be
differentially affected by restricted auditory access. DESIGN: The
vocalizations
and early verbalizations of 21 infants with normal hearing and 12
early-identified infants with hearing loss were compared over a period
of 14 mo
(from 10 to 24 mo of age). Thirty-minute mother-child interaction
sessions were
video recorded at 6- to 8-wk intervals in a laboratory playroom
setting. Syllable
complexity changes and consonantal development were quantified from
vocalizations
and early verbalizations. Early behaviors were related to speech
production
measures at 36 mo of age. Participants with hearing loss were recruited
from
local audiology clinics and early intervention programs. Participants
with normal
hearing were recruited through day care centers and pediatrician
offices.
RESULTS: Relative to age-matched, normal-hearing peers, children with
hearing
loss were delayed in the onset of consistent canonical babble. However,
certain
children with moderately-severe losses babbled on time, and infants
with cochlear
implants babbled within 2 to 6 mo of implantation. The infants with
hearing loss
had smaller consonantal inventories and were slower to increase
syllable shape
complexity than age-matched normal-hearing peers. The overall pattern
of results
suggested that consonant development in infants with hearing loss was
delayed but
not qualitatively different from children with normal hearing. Delays
appeared to
be less pronounced than suggested by previous research. However,
fricative/affricate development progressed slowly in infants with
hearing loss
and divergence from the patterns of normal-hearing children was
observed. Six
children (2 with normal hearing; 4 with hearing loss) were identified
as
atypical, based on their rates of development. At 24 mo of age, these
children
persisted in producing a high proportion (0.59) of vocalizations
lacking
consonants, which was negatively correlated with Goldman-Fristoe scores
at 36 mo
(r = -0.60). CONCLUSIONS: Results suggest that early-identified
children are
delayed in consonant and syllable structure development, which may
influence
early word learning rates. Fricative/affricate development appears to
be
challenging for some infants with hearing loss. This may be related to
the
effects of sensorineural hearing loss on high-frequency information,
restricted
bandwidth provided by amplification, and reduced audibility in contexts
of noise
and reverberation. Delayed fricative use may have implications for
morphological
development. Atypically slow rates of change in syllable development
may indicate
that a child is at risk for delayed speech development.
Publication Types:
Research Support, N.I.H., Extramural
PMID: 17804976 [PubMed - indexed for MEDLINE]
27: J Inherit Metab Dis. 2007 Aug;30(4):445-6.
Scene from the USA: the illogic of mandating screening without also
providing for
treatment.
Buist NR, Huntington K.
Publication Types:
Editorial
PMID: 17805992 [PubMed - indexed for MEDLINE]
28: Hear Res. 2007 Nov;233(1-2):86-96. Epub 2007 Aug 8.
Click-evoked otoacoustic emissions (CEOAEs) recorded from neonates
under 13 hours
old using conventional and maximum length sequence (MLS) stimulation.
de Boer J, Brennan S, Lineton B, Stevens J, Thornton AR.
MRC Institute of Hearing Research, Southampton Outstation, Royal South
Hants
Hospital, Brintons Terrace, Mailpoint OAU, Southampton, Hampshire SO14
OYG, UK.
[log in to unmask]
Maximum length sequence (MLS) stimulation allows click evoked
otoacoustic
emissions (CEOAEs) to be averaged at very high stimulation rates. This
enables a
faster reduction of noise contamination of the response, and has been
shown to
improve the signal-to-noise ratio (SNR) of CEOAEs recorded from adult
subjects.
This study set out to investigate whether MLS averaging can enhance the
SNR of
CEOAEs recorded in newborns within the first day after birth, and so
improve the
pass rates for OAE screening in this period, when false alarm rates are
very
high. CEOAEs were recorded in a neonatal ward from 57 ears in 37
newborns ranging
from 6 to 13h old, using both conventional (50/s) and high rate
(5000/s) MLS
averaging. SNR values and pass rates were compared for responses
obtained within
equal recording times at both rates. MLS averaging produced an SNR
improvement of
up to 3.8dB, with the greatest improvement found in higher frequency
bands. This
SNR advantage resulted in pass rate improvement between 5% and 10%,
depending on
pass criterion. A significant effect of age was found on both SNR and
pass rate,
with newborns between 6 and 10h old showing significantly lower values
than those
tested between 10 and 13h after birth, as well as a much greater
improvement due
to MLS averaging. The findings show that MLS averaging can reduce false
alarm
rates by up to 15% in very young neonates in a neonatal ward setting.
PMID: 17850998 [PubMed - indexed for MEDLINE]
29: J Inherit Metab Dis. 2007 Oct;30(5):818. Epub 2007 Sep 17.
Combination of enzyme analysis, allele-specific PCR and sequencing to
detect
mutations in the GALT gene.
Calderon FR, Nelson L, Dobrowolski P, Sinitsyna I, Phansalkar A, Longo
N,
Pasquali M, Mao R.
ARUP Institute for Clinical and Experimental Pathology, Salt Lake City,
UT 84108,
USA.
Newborn screening can identify patients with classical galactosaemia,
and their
diagnosis needs to be confirmed with assay of the activity of
galactose-1-phosphate uridyltransferase (GALT). Unfortunately, in many
cases the
results can be ambiguous and further testing is required. Here we
report a
combination of biochemical analysis of GALT enzyme activity and
mutation analysis
of the most common mutations in the corresponding gene. Samples (n =
243)
submitted for confirmatory testing for classical galactosaemia were
analysed
simultaneously for GALT enzyme activity and allele-specific
PCR/fragment analysis
for seven mutations and two polymorphisms in the GALT gene (mutations
IVS2-2A>G,
p.S135L, p.T138M, p.L195P, p.K285N, p.Q188R, p.Y209C; polymorphisms
p.N314D,
p.L218L). Mutation detection accorded with biochemical analysis in 93%
of
samples. Subsequently, a total of 34 samples with either discordant
results
between the above methods or low enzyme activity were fully sequenced,
identifying previously reported pathogenic mutations and seven novel
variations
(p.P185H, p.R201C, p.E220K, p.R223S, p.I278N, p.L289F and p.L218X) in
the GALT
gene. This approach further increased concordance between genetic and
biochemical
analysis to 99% of all alleles tested. Our results indicate that DNA
testing can
help to verify biochemical enzymatic data and improve distinction of
borderline
enzyme activities where a patient may still benefit from treatment.
Publication Types:
Research Support, Non-U.S. Gov't
PMID: 17876724 [PubMed - indexed for MEDLINE]
30: Can J Public Health. 2007 Jul-Aug;98(4):284-6.
Newborn screening by tandem mass spectrometry: ethical and social
issues.
Avard D, Vallance H, Greenberg C, Potter B.
Centre de recherche en droit public, Université de Montréal, C.P. 6128,
succ.
Centre-ville, Montreal, QC H3C 3J7. [log in to unmask]
Emerging technologies like Tandem Mass Spectrometry (TMS) enable
multiple tests
on a single blood sample and allow the expansion of Newborn Screening
(NBS) to
include various metabolic diseases. Introducing TMS for NBS raises
important
social and ethical questions: what are the criteria for adding
disorders to
screening panels? What evidence justifies expansion of screening? How
can equity
in NBS access and standards be ensured? How can policy standards be
set, given
the multiplicity of stakeholders? To address emerging issues,
policy-makers,
patient advocates, clinicians and researchers had a workshop during the
2005
Garrod Symposium. The participants received a summary of the discussion
and
understood the workshop's goal was to provide a basis for further
discussion.
This article contributes to this ongoing discussion. Several proposed
recommendations assert the centrality of including social and ethical
issues in
the assessment of whether or not to introduce TMS. The article outlines
five key
recommendations for advancing the NBS agenda: national public health
leadership;
transparency; increased national consistency in NBS strategy, including
minimum
standards; collaboration between the federal and
provincial/territorial
governments and diverse stakeholders; and supporting research and/or
programs
based on effectiveness, which integrate ethical and social issues into
assessment.
Publication Types:
Research Support, Non-U.S. Gov't
PMID: 17896737 [PubMed - indexed for MEDLINE]
31: J Mol Neurosci. 2007 Sep;33(1):105-13.
"Lorenzo's oil" therapy for X-linked adrenoleukodystrophy: rationale
and current
assessment of efficacy.
Moser HW, Moser AB, Hollandsworth K, Brereton NH, Raymond GV.
Department of Neurogenetics, Kennedy Krieger Institute, Baltimore, MD,
USA.
X-linked adrenoleukodystrophy (X-ALD) is a genetic disorder that
damages the
nervous system and is associated with the accumulation of saturated
very long
chain fatty acids (SVLCFA). Oral administration of "Lorenzo's oil"
(LO), a 4:1
mixture of glyceryl trioleate and glyceryl trierucate, normalizes the
SVLCFA
levels in plasma, but its clinical efficacy and the clinical
indications for its
use have been controversial for more than 15 years. We review the
biochemical
effects of LO administration and the rationale for its use and present
a current
appraisal of its capacity to reduce the risk for the childhood cerebral
phenotype
when administered to asymptomatic boys and to slow progression of
adrenomyeloneuropathy in patients without cerebral involvement. We also
present
current efforts to provide definitive evaluation of its clinical
efficacy and
discuss its possible role in the new therapeutic opportunities that
will arise if
newborn screening for X-ALD is validated and implemented.
PMID: 17901554 [PubMed - in process]
32: Arch Pediatr Adolesc Med. 2007 Oct;161(10):994-1000.
Long-term follow-up data collection and use in state newborn screening
programs.
Hoff T, Ayoob M, Therrell BL.
Department of Health Policy, Management, and Behavior, School of Public
Health,
State University of New York at Albany, 1 University Pl, Rensselaer, NY
12144,
USA. [log in to unmask]
OBJECTIVES: To describe and analyze the types of data-related policies
and
practices that currently exist among state newborn screening (NBS)
programs in
relation to long-term follow-up (LTFU) and oversight for newborns with
confirmed
disorders. DESIGN: A 19-question online survey. PARTICIPANTS:
Thirty-five state
NBS programs. MAIN OUTCOME MEASURES: Whether LTFU is performed,
collection and
use of LTFU data, and variety of LTFU data collected. RESULTS: Survey
findings
reveal data-related challenges faced by state NBS programs in their
ability to
perform ongoing oversight, evaluation, and quality assurance with
respect to LTFU
for newborns with confirmed disorders. Of the NBS programs surveyed,
56% reported
collecting no LTFU data. More than two-thirds of state NBS programs
surveyed do
not use LTFU data at all or use it only minimally. Most programs that
collect any
LTFU data from providers (physicians, nurses, and allied health
professionals) do
it through verbal communication or paper forms rather than
electronically. Almost
half of the programs collecting any LTFU data do so only once a year. A
lot of
variety exists in the types of LTFU data collected across programs.
Most of the
15 programs that reported collecting LTFU data use it to track the
clinical
outcomes of patients, assess the needs of patients and their families
for
services, and track and identify individuals lost to follow-up across
time.
CONCLUSION: The results generally point to a need for greater alignment
of state
NBS program data practices and policies with the data requirements for
essential
public health functions, such as quality assurance, program evaluation,
and
cost-benefit analysis.
PMID: 17909144 [PubMed - indexed for MEDLINE]
33: J Inherit Metab Dis. 2007 Oct 5 [Epub ahead of print]
Complete recovery from acute encephalopathy of late-onset ornithine
transcarbamylase deficiency in a 3-year-old boy.
Mak CM, Siu TS, Lam CW, Chan GC, Poon GW, Wong KY, Low LC, Tang NL, Li
SK, Lau
KY, Kwong NS, Tam S.
Division of Clinical Biochemistry, Queen Mary Hospital, Hong Kong, SAR,
China,
[log in to unmask]
Ornithine transcarbamylase deficiency is the commonest urea cycle
disorder which
is transmitted in X-linked inheritance. It is mainly characterized in
males by
acute encephalopathy and hyperammonaemia with fatal outcomes in both
classical
neonatal and late-onset types. We report a 3-year-old healthy Hong Kong
Chinese
boy who presented with acute encephalopathy and coma after three days
of
gastroenteritis. He had no focal neurological deficit and brain CT
imaging was
normal. His plasma ammonia (54 mumol/L) and glutamine (747 mumol/L)
concentrations were normal. The only biochemical abnormalities detected
were
marked orotic aciduria (700 mumol/mmol creatinine) and elevated urinary
uracil.
He regained consciousness spontaneously after three days under
intensive care
with parenteral fluid therapy. He recovered completely without any
neurological
deficits. Five months after discharge, urinary uracil concentration
remained
elevated despite normalized orotic acid concentration. Finally,
ornithine
transcarbamylase deficiency was diagnosed by DNA analysis. A missense
mutation of
arginine-to-glutamine substitution on amino acid 277 (p.R277Q) was
revealed to be
a late-onset mutant. Our case strengthens the argument that in any
child with
coma or acute encephalopathy of undetermined cause, genetic analysis of
the OTC
gene and the measurement of urinary uracil concentration remain the
most reliable
indicators of late-onset OTCD during acute and even quiescent phases.
Existing
neonatal screening programmes for inheritable metabolic disorders fail
to detect
late-onset variants. Therefore, a high clinical suspicion is a key to
correct and
timely diagnosis, especially in those patients with atypical
presentations.
PMID: 17922216 [PubMed - as supplied by publisher]
34: J Inherit Metab Dis. 2007 Oct 8 [Epub ahead of print]
Description of the mutations in 15 subjects with variant forms of maple
syrup
urine disease.
Flaschker N, Feyen O, Fend S, Simon E, Schadewaldt P, Wendel U.
Department of General Paediatrics, University Children*s Hospital,
Heinrich-Heine-University, Düsseldorf, Germany.
BACKGROUND: In maple syrup urine disease (MSUD), disease-causing
mutations can
affect the BCKDHA, BCKDHB or DBT genes encoding for the E1alpha, E1beta
and E2
subunits of the multienzyme branched-chain 2-keto acid dehydrogenase
(BCKD)
complex. AIM: The aim of this study was to screen DNA samples of 15
subjects with
distinct well-characterized variant MSUD phenotypes for mutations in
the three
genes in order to demonstrate a potential correlation between specific
nucleotide
changes and particular variant phenotypes. METHODS: The exonic coding
sequences
of all three genes were studied using genomic DNA and cellular RNA
derived from
peripheral blood leukocytes. RESULTS: In 37% of the cases (total 30
alleles),
disease-causing mutations were located in the BCKDHA, in 46% in the
BCKDHB, and
in 13% in the DBT gene. Novel mutations occurring homozygously were
p.Ala328Thr
in the BCKDHA gene and p.Gly249_Lys257del in the DBT gene. Both are
associated
with a mild MSUD variant. The same holds true for the novel mutations
p.Pro200Ala
in BCKDHB and p.Phe307Ser in DBT which were identified in heterozygous
fashion.
Among the known mutant alleles, p.Gly278Ser in the BCKDHB gene was
relatively
frequent and also associated with a mild MSUD variant. CONCLUSION: The
results of
this study indicate that genotyping may be predictive of clinical
severity of
variant MSUD phenotypes and might be of prognostic value particularly
in subjects
with variant MSUD identified in newborn screening in whom early
treatment
fortunately slows the natural course of the disease.
PMID: 17922217 [PubMed - as supplied by publisher]
35: J Paediatr Child Health. 2007 Nov;43(11):721-3.
Community-wide screening for cystic fibrosis carriers could replace
newborn
screening for the diagnosis of cystic fibrosis.
Massie J, Forbes R, Dusart D, Bankier A, Delatycki MB.
Department of Respiratory Medicine, Royal Children's Hospital,
Parkville,
Victoria, Australia. [log in to unmask]
Most babies with cystic fibrosis (CF) are born to parents who did not
know they
were carriers until their baby was diagnosed with CF, usually by
newborn
screening. It is only after the birth of their first child with CF that
couples
are offered genetic counselling and reproductive choices. Most use
this
information for prenatal testing of subsequent pregnancies. With the
high uptake
of first trimester screening for Down syndrome (80% in Victoria) most
couples
have had screening during the CF affected pregnancy. Yet screening for
CF carrier
status is available, costs are similar to that for Down syndrome
screening and CF
carrier screening only ever needs to be done once. Waiting for couples
to have a
baby with CF before they are identified as carriers denies them choice.
A
national policy on CF carrier screening in Australia, and determination
to
equitably fund such a programme, is required.
PMID: 17924936 [PubMed - in process]
36: J Med Screen. 2007;14(3):123-31.
The impact of newborn hearing screening on communication development.
Fitzpatrick E, Durieux-Smith A, Eriks-Brophy A, Olds J, Gaines R.
Children's Hospital of Eastern Ontario Research Institute, Ottawa,
Canada.
[log in to unmask]
OBJECTIVE: Universal newborn hearing screening has become standard
practice in
many countries. The primary goal of this study was to assess the impact
of early
identification of permanent childhood hearing loss on oral
communication
development. SETTING: Participants were recruited from three clinical
programmes
in two cities in the province of Ontario, Canada. The study sample was
born
during two consecutive periods of newborn hearing screening. The first
period,
prior to 2002, was targeted on high-risk infants only, and the second,
from 2002,
included both high- and standard-risk infants (universal newborn
hearing
screening - UNHS). All children were enrolled in rehabilitation
programmes
focused on oral language development. METHODS: In this multicentre
observational
study, 65 children under the age of five years with onset of hearing
loss before
six months of age, 26 identified through systematic newborn screening
(14 through
targeted screening and 12 through UNHS) and 39 without screening, were
assessed
with an extensive battery of child- and parent-administered speech and
language
measures. The degree of hearing loss ranged from mild to profound with
22
children in the mild, moderate and moderately severe categories and 43
in the
severe and profound categories. Data are reported for the three-year
study
period. RESULTS: The screened group of children was identified at a
median age of
6.6 (interquartile range, 3.0-8.2) months and children referred from
sources
other than newborn screening were diagnosed at a median age of 16.5
(interquartile range, 10.2-29.0) months. Assessment of oral
communication
development showed no significant difference between the screened and
unscreened
groups. The communication outcomes for children identified before 12
months of
age did not differ from those of later identified children.
CONCLUSIONS:
Systematic screening of newborn hearing results in earlier
identification and
intervention for children with permanent hearing loss. Superior
language outcome
following newborn screening was not demonstrable in the setting of this
study.
Publication Types:
Research Support, Non-U.S. Gov't
PMID: 17925084 [PubMed - in process]
37: Aust Fam Physician. 2007 Oct;36(10):794-800.
Population genetic screening.
Metcalfe SA, Barlow-Stewart K, Delatycki MB, Emery J.
Genetics Education and Health Research, Murdoch Childrens Research
Institute,
Melbourne, Victoria. [log in to unmask]
BACKGROUND: Genetic screening programs in Australia are primarily
carried out
during pregnancy for maternal thalassaemia carrier status, chromosomal
conditions
and neural tube defects in the fetus, and for a number of conditions in
the
newborn. OBJECTIVE: This article describes these programs and the
general
practitioner's role, particularly around offering prenatal screening
that
includes nongenetic aspects (eg. smoking, alcohol), to enable good
practice.
DISCUSSION: General practitioners can be involved in offering prenatal
screening
and in giving increased risk results from prenatal and newborn
screening, with
due consideration of informed decision making and counselling about the
meaning
of the result. Increased risk results from these screening programs are
followed
up by further testing where required. As genetic contribution to
diseases,
especially complex common conditions, becomes better understood, more
genetic
tests will become available. This may impact on the role of the GP in
population
genetic screening programs.
PMID: 17925898 [PubMed - in process]
38: J Allergy Clin Immunol. 2007 Oct;120(4):753-5.
Primary immunodeficiency: meeting the challenges.
Shearer WT, Malech HL, Puck JM.
Publication Types:
Editorial
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
PMID: 17931558 [PubMed - indexed for MEDLINE]
39: J Allergy Clin Immunol. 2007 Oct;120(4):760-8.
Population-based newborn screening for severe combined
immunodeficiency: steps
toward implementation.
Puck JM; SCID Newborn Screening Working Group.
Department of Pediatrics, University of California, San Francisco, CA
94143-0519,
USA. [log in to unmask]
Severe combined immune deficiency (SCID) has been identified as a
disorder of
high priority for population-based newborn screening. Most affected
infants are
not brought to medical attention until they develop serious infectious
complications, and SCID is fatal if untreated. Effective treatment
with
allogeneic hematopoietic stem cell transplantation is widely
established. The
best outcome for SCID, as with many other conditions for which newborn
screening
is now done, is achieved if hematopoietic stem cell transplantation is
performed
in the first months of life, ideally before clinical presentation with
infections
and failure to thrive. A meeting in San Francisco in May 2007 brought
together
experts from newborn screening programs; the pediatric immunology
community;
pediatric transplant centers; and federal, state, and nongovernmental
agencies to
consider obstacles to and implications of developing newborn screening
for SCID.
Development of an appropriate low-cost, high-throughput screening
algorithm has
been a challenge, although absence of T-cell receptor gene excision
circles is a
sensitive marker of profound T lymphocytopenia and currently is the
most
developed screening method. A consensus was reached on several points:
SCID
newborn screening should be pursued with pilot studies in key locales,
test
methodologies need to be optimized, screening programs must be
integrated with
plans for definitive diagnosis and management, centralized specimen
banks and
registries are required to foster test validation and track outcomes
that will
guide future treatment, and SCID newborn screening will lead to
important
knowledge about human immune disorders as well as better care of
patients.
Publication Types:
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
PMID: 17931561 [PubMed - indexed for MEDLINE]
40: Paediatr Perinat Epidemiol. 2007 Nov;21(6):525-31.
Congenital toxoplasmosis: late pregnancy infections detected by
neonatal
screening and maternal serological testing at delivery.
Lago EG, Neto EC, Melamed J, Rucks AP, Presotto C, Coelho JC, Parise C,
Vargas
PR, Goldbeck AS, Fiori RM.
Department of Pediatrics, Pontifícia Universidade Católica do Rio
Grande do Sul,
Porto Alegre, Brazil. [log in to unmask]
The first aim of this study was to determine the prevalence of
congenital
toxoplasmosis in newborn infants treated by the public health system in
Porto
Alegre, a city in southern Brazil, using neonatal screening for
Toxoplasma
gondii-specific IgM. The second aim was to investigate whether the
cases detected
by this approach could have been identified by the prenatal screening
for
antibodies to T. gondii that was performed in the same population. A
fluorometric
assay was used to analyse T. gondii-specific IgM in filter paper
specimens
obtained from newborn infants for routine screening for metabolic
diseases. When
the specific IgM was positive, serum samples from the infant and the
mother were
requested for confirmatory serological testing, and the infant
underwent clinical
examination. Among 10 000 infants screened for T. gondii-specific IgM,
seven
filter paper samples were positive, and congenital toxoplasmosis was
confirmed in
six patients. The prevalence of IgM specific for T. gondii was 6/10 000
[95% CI
2/10 000, 13/10 000]. One infected infant had already been identified
in the
maternity ward before birth, three had been identified by maternal
serology at
delivery, and two infants with congenital toxoplasmosis were identified
solely
through neonatal screening. Although four mothers of the patients with
congenital
toxoplasmosis received prenatal care, and three mothers had one or two
serological tests for T. gondii-specific antibodies (one at first
trimester, one
at first and second trimesters, and the other at second and third
trimesters),
they were not identified during pregnancy as infected. Neonatal
screening
identified cases of infection not detected by obtaining only one or two
serum
samples from pregnant women for T. gondii serology, mainly when
infection was
acquired and transmitted in late pregnancy. Maternal serology at
delivery and
neonatal screening were especially useful in the identification of
infants with
congenital toxoplasmosis when the mother did not receive regular
prenatal
serological testing or prenatal care.
Publication Types:
Research Support, Non-U.S. Gov't
PMID: 17937738 [PubMed - in process]
41: Nat Rev Genet. 2007 Nov;8(11):828.
Carrier testing in minors: conflicting views.
Borry P, Nys H, Dierickx K.
PMID: 17943191 [PubMed - indexed for MEDLINE]
42: Minerva Pediatr. 2007 Aug;59(4):307-13.
Early hearing detection and intervention in children with prelingual
deafness,
effects on language development.
Bubbico L, Di Castelbianco FB, Tangucci M, Salvinelli F.
Department of Otolaryngology, Italian Institute of Social Medicine,
Rome, Italy.
[log in to unmask]
AIM: The purpose of this study was to assess, the cognitive and
receptive
language abilities in children with prelingual hearing impairment, in
relation to
the age of enrollment in the intervention program and examine the
related
variables. METHODS: Seventy children with congenital prelingual
deafness were
divided into 2 groups based on their age at the start of the
intervention
program: 17 children enrolled between 0-12 months of age, 53 children
enrolled
after the age of 12 months. The age of intervention is defined as the
identification and confirmation of hearing loss, adaptation of hearing
aids, and
enrollment in the program of special education at the Orthophonological
Institute
of Rome. Assessments were carried out at 5 years of age. The receptive
language
abilities were measured using the Peabody picture vocabulary test
(PPVT), while
the cognitive abilities used the Raven standard progressive matrices
test. The
material was administered by staff skilled in assessing children with
hearing
loss. The assessment of language score tests (PPVT and Raven
progressive matrix
test) of samples of children with hearing loss was compared with
normal
standardized scores of hearing peers at 5 years of age. Mean group
differences
were compared using t-tests. The results were considered statistically
significant for a P-value less than or equal to 0.05. RESULTS: A
progressive
decline in the mean PPVT score with increasing ages of enrollment was
present.
The mean receptive language score of the children enrolled within the
first 12
months was significantly better (P<0.001) compared to those over 13
months. The
nonverbal IQ, determined by Raven's standard progressive matrices,
showed no
statistically significant differences in IQ scores (P = 0.083) between
children
with early and late age of enrollment. Our data revealed that language
abilities
are significantly affected by the degree of hearing loss (P<0.001
Children with
very severe hearing loss, find it more difficult to achieve adequate
language
abilities than children with moderate and severe hearing. CONCLUSION:
According
to previous studies on the matter, our data suggest that identification
of
hearing loss at early age associated with early hearing aid fitting,
and
enrollment in early intervention within the first 12 months of age, may
help to
obtain good results in the receptive language skills performance. The
early
identification of prelingual hearing loss at birth through the neonatal
screening
must therefore be, , considered the primary step for accessing a
quality
intervention.
PMID: 17947837 [PubMed - in process]
43: Otol Neurotol. 2007 Sep;28(6):788-92.
reducing false positives in newborn hearing screening program: how and
why.
Lin HC, Shu MT, Lee KS, Lin HY, Lin G.
Department of Otolaryngology, Hearing & Speech Center, Mackay Memorial
Hospital,
Taipei, Taiwan. [log in to unmask]
OBJECTIVE: To compare the initial referral rate, the accurate
identification rate
of congenital hearing loss, and the cost between one step with
transient evoked
otoacoustic emissions (TEOAEs), two steps with TEOAE and automated
auditory
brainstem response (AABR), and one step with AABR in newborn hearing
screening
program. The aim of this study is to compare their efficacy between our
three
different protocols and to see which one is most cost-effective. STUDY
DESIGN:
From November 1998 to April 2006, 25,588 healthy newborns were screened
for
hearing loss in Mackay Memorial Hospital, Taipei. In the periods from
November
1998 to January 2004, from February 2004 to February 2005, and from
March 2005 to
April 2006, the screening tools used were TEOAE alone (n = 18,260),
TEOAE plus
AABR (n = 3,540), and AABR (n = 3,788), respectively. RESULTS: A
statistically
significant decrease in referral rate was achieved in the group using
AABR as
screening tools when compared with TEOAE plus AABR and TEOAE alone (0.8
versus
1.6 versus 5.8%). The accurate identification rate of congenital
hearing loss was
0.42% in AABR protocol, 0.25% in TEOAE and AABR protocol, and 0.45% in
TEOAE
protocol, which was not statistically significant. The total direct
costs
(including predischarge screening and postdischarge follow-up costs)
per
screening were US $10.04 for the program using TEOAE alone, US $8.60
for TEOAE
plus AABR, and US $7.33 for AABR. The intangible cost (parental
anxiety) was much
higher in the earlier program due to higher referral rate. CONCLUSION:
In the
efficacy of the hearing screening program using the one-step TEOAE,
two-step
TEOAE and AABR, and one-step AABR programs, the latter significantly
decreased
the referral rate from 5.8, to 1.6, and to 0.8%. No significant
difference was
noted between their accurate identification rates of congenital hearing
loss. The
total costs, including expenditures and intangible cost, were much
lower in the
protocol with AABR due to reduction in false positives.
Publication Types:
Comparative Study
PMID: 17948357 [PubMed - indexed for MEDLINE]
44: Genet Test. 2007 Fall;11(3):296-302.
Attitudes of families affected by adrenoleukodystrophy toward prenatal
diagnosis,
presymptomatic and carrier testing, and newborn screening.
Schaller J, Moser H, Begleiter ML, Edwards J.
Myriad Genetic Laboratories, Inc., Medical Services, Salt Lake City, UT
84108,
USA. [log in to unmask]
Families affected by adrenoleukodystrophy (ALD) and
adrenomyeloneuropathy (AMN)
were surveyed to elicit attitudes toward prenatal, presymptomatic and
carrier
testing, and newborn screening in order to determine the level of
support that
these families have for current and future genetic testing protocols.
Identifying
attitudes toward genetic testing, including newborn screening, is
especially
important because of new data regarding therapeutic options and the
possible
addition of ALD to newborn screening regimens. The Kennedy Krieger
Institute
(KKI) database identified 327 prospective participants. Families that
were
willing to participate in the study received an anonymous questionnaire
for
completion. Frequencies were generated using SPSS software for
Windows.
Questionnaires were returned from 128 families for a response rate of
39%. Sons
who were at risk for inheriting the ALD gene would be tested by 93% of
respondents, and 89.3% would ideally have this testing performed
prenatally or in
the newborn period. Eighty-nine percent would test an at-risk daughter
and 51.2%
would ideally have this testing performed prenatally or shortly after
birth. ALD
newborn screening for males and females was supported by 90% of
respondents. If
newborn screening for ALD/AMN commences, or there is a new diagnosis of
ALD,
genetic professionals need to be prepared to have extensive
conversations with
families regarding the benefits and limitations of current therapeutic
and
genetic testing options.
PMID: 17949291 [PubMed - in process]
45: J Clin Virol. 2007 Oct 22 [Epub ahead of print]
Congenital cytomegalovirus (CMV) infection as a cause of permanent
bilateral
hearing loss: A quantitative assessment.
Grosse SD, Ross DS, Dollard SC.
National Center on Birth Defects and Developmental Disabilities,
Centers for
Disease Control and Prevention, USA.
BACKGROUND: Congenital cytomegalovirus (CMV) infection is a cause of
sensorineural hearing loss (SNHL) in children, but the magnitude of
its
contribution is uncertain. Quantifying the impact of congenital CMV
infection
requires an evidence-based assessment using a standard case definition
of hearing
loss. OBJECTIVES: To determine the frequency of bilateral moderate to
profound
SNHL in children with congenital CMV infection and to estimate the
CMV-attributable fraction of bilateral moderate to profound SNHL. STUDY
DESIGN: A
systematic review of studies of children with congenital CMV infection
ascertained in an unbiased manner through universal newborn screening
for CMV
using viral culture in urine or saliva specimens in combination with a
review of
the literature on congenital CMV infection and hearing loss, including
articles
of all types. RESULTS: Approximately, 14% of children with congenital
CMV
infection develop SNHL of some type, and 3-5% develop bilateral
moderate to
profound SNHL. Among all children with bilateral moderate to profound
SNHL, we
estimate that 15-20% of cases are attributable to congenital CMV
infection.
CONCLUSIONS: Congenital CMV infection is one of the most important
causes of
hearing loss in young children, second only to genetic mutations, and
is
potentially preventable.
PMID: 17959414 [PubMed - as supplied by publisher]
46: Pediatrics. 2007 Nov;120(5):e1327-34.
Newborn screening for Pompe disease: synthesis of the evidence and
development of
screening recommendations.
Kemper AR, Hwu WL, Lloyd-Puryear M, Kishnani PS.
Program on Pediatric Health Services Research, Department of
Pediatrics, Duke
University, Durham, North Carolina, USA. [log in to unmask]
BACKGROUND: Pompe disease is a lysosomal storage disorder that leads to
the
accumulation of glycogen and subsequently to muscle weakness, organ
damage, and
death. Pompe disease is detectable through newborn screening, and
treatment has
become available recently. OBJECTIVE: Our goal was to review
systematically all
available evidence regarding screening for infantile Pompe disease to
help policy
makers determine whether Pompe disease should be added to their state's
newborn
screening battery. METHODS: We searched online databases, including
Medline,
clinicaltrials.gov, and the Computer Retrieval of Information on
Scientific
Projects database, as well as Web sites maintained by federal
organizations (eg,
the Food and Drug Administration) and other nonprofit or private
organizations
(eg, the March of Dimes and Genzyme Corp), by using the terms "glycogen
storage
disease type II," "Pompe disease," and "Pompe's disease." We also
obtained
preliminary findings from a screening program in Taiwan. Data were
critically
appraised and extracted by 2 investigators, one who is an expert in
systematic
review methods and the other who is an expert in Pompe disease.
RESULTS: The
prevalence of Pompe disease has been estimated to be approximately 1
case per
40,000. Small studies suggest that enzyme therapy is highly efficacious
in
infantile Pompe disease and that earlier intervention leads to improved
outcomes.
Screening cannot distinguish between infantile and late-onset Pompe
disease. The
current screening program in Taiwan has a high false-positive rate;
however, the
threshold was purposely set low to ensure that no case would be
missed.
CONCLUSIONS: Pilot studies of screening are needed to identify the
most
efficacious strategy for screening and determine how to manage cases
of
late-onset Pompe disease before screening for Pompe disease is adopted
widely by
newborn screening programs.
Publication Types:
Research Support, U.S. Gov't, P.H.S.
Review
PMID: 17974725 [PubMed - in process]
47: Mol Genet Metab. 2007 Oct 30 [Epub ahead of print]
Risk of sudden death and acute life-threatening events in patients with
glutaric
acidemia type II.
Angle B, Burton BK.
Division of Birth Defects and Metabolism, Department of Pediatrics,
Children*s
Memorial Hospital, Northwestern University, Feinberg School of
Medicine, 2300
Children*s Plaza, Box 59, Chicago, IL 60614, USA.
Glutaric acidemia type II (GAII) is an inborn error of metabolism
caused by
defects in electron transport flavoprotein (ETF) or ETF-ubiquinone
oxidoreductase
(ETF-QO) and typically presents with hypo- or nonketotic hypoglycemia
and
metabolic acidosis. The most severe forms present in early infancy and
are
associated with a high mortality rate. The disorder can now be detected
by
expanded newborn screening using tandem mass spectrometry (MS/MS),
providing the
opportunity for diagnosis and treatment in asymptomatic infants. We
report here
three infants who, despite diagnosis and treatment in the neonatal
period,
experienced either unexpected sudden death or an acute life-threatening
event
(ALTE) during the first year of life. The possible etiologies of these
events and
the potential impact of expanded newborn screening on the long-term
outcome of
GAII are discussed.
PMID: 17977044 [PubMed - as supplied by publisher]
48: Int J Audiol. 2007 Nov;46(11):686-91.
Call for calibration standard for newborn screening using auditory
brainstem
responses.
Durrant JD, Sabo DL, Delgado RE.
Department of Communication Science and Disorders, Pittsburgh, USA.
The mode of stimulation employed in newborn screening of the auditory
brainstem
response has evolved from the clinically standardized supraaural
earphone to the
tubal insert earphone, to most recently a circumaural earphone
developed for this
test. Considered here is the need to develop a standard for calibration
of such
devices for newborn screening applications, in particular. At risk is
the
prospect of missing the milder degrees of hearing loss, assuming a goal
of
detecting all clinically-significant congenital hearing losses. Two
commercially
manufactured test instruments for automated newborn screening were
scrutinized
via bench testing of sound output from their respective transducers,
using a
variety of measurements. By convention or design, none of the
measurement
approaches involved a model of the newborn ear, per se. While it was
concluded
that the manufacturers' method shows promise, namely as a relatively
simple and
potentially reliable method of calibration, concerns arose regarding
output
levels when measured according to both the manufacturers' and the
authors'
methods. Further work is needed to critically assess calibration
methods and to
establish, to the extent possible, appropriate norms and validation
studies in
newborns to provide a better understanding of the actual sound pressure
level of
the screening stimulus.
PMID: 17978951 [PubMed - in process]
49: Mol Genet Metab. 2007 Nov 5 [Epub ahead of print]
Glutaric aciduria type 2 and newborn screening: Commentary.
Vockley J.
University of Pittsburgh, School of Medicine and Graduate School of
Public
Health, Departments of Pediatrics and Human Genetics, Children*s
Hospital of
Pittsburgh, 3705 Fifth Avenue, Pittsburgh, PA 15238, USA.
Glutaric aciduria type 2 is increasingly being identified through
expanded
newborn screening programs by tandem mass spectrometry with a goal of
decreasing
morbidity and mortality. This article presents 3 patients with adverse
outcomes
in spite of early recognition by newborn screening. Additional long
term studies
are necessary to determine the efficacy of newborn screening to affect
outcome in
this disorder.
PMID: 17988913 [PubMed - as supplied by publisher]
50: Curr Opin Allergy Clin Immunol. 2007 Dec;7(6):522-7.
Neonatal screening for severe combined immune deficiency.
Puck JM.
Department of Pediatrics and Institute for Human Genetics, University
of
California San Francisco, San Francisco, California, USA.
PURPOSE OF REVIEW: Severe combined immunodeficiency has been identified
as a
high-priority disease for inclusion in population-based newborn
screening
programs. In this review, the justification, advances to date and
remaining
challenges for universal severe combined immunodeficiency screening are
outlined.
RECENT FINDINGS: Severe combined immunodeficiency is treatable by
hematopoietic
stem cell transplantation, with best outcome if recognized and treated
early in
life. Universal screening of newborns could make possible prompt
diagnosis and
lifesaving treatment for all affected infants. One screening test using
the dried
blood spots already collected from all newborns involves quantitation
of T cell
receptor excision circles, and other test methods have been proposed
and are
being evaluated. Development of screening programs will require
integration of
screening, contacting infants with abnormal screen results for
definitive
testing, prompt treatment of affected infants, and outcome tracking.
SUMMARY:
Newborn screening for severe combined immunodeficiency is advancing
toward pilot
trials.
PMID: 17989529 [PubMed - in process]
51: J Pediatr (Rio J). 2007 Nov;83(5 Suppl):S209-16. Epub 2007 Nov 14.
Hypothyroidism in children: diagnosis and treatment.
Setian NS.
Faculdade de Medicina, Universidade de São Paulo (USP), São Paulo, SP,
Brazil.
OBJECTIVE: To present relevant and updated information on the status
of
hypothyroidism in the pediatric population (newborn infants to
adolescents).SOURCES: Original and review articles and books containing
relevant
updated data.SUMMARY OF THE FINDINGS: This review addressed data on
the
etiopathogeny of hypothyroidism and on the importance of screening for
congenital
hypothyroidism to assure early diagnosis and treatment of the newborn.
We point
out the difficulties experienced in the handling of subclinical
hypothyroidism;
we also address the importance of diagnosing autoimmune Hashimoto's
thyroiditis,
the high incidence of the disease among adolescents, mainly females,
and the
occurrence of a severe neurological condition, Hashimoto's
encephalopathy. We
indicate situations in which severe hypothyroidism may lead to puberty
disorders
(precocious or delayed puberty) and describe the importance of
transcription
factors in thyroid embryogenesis. Diagnostic and therapeutic criteria
are also
addressed.CONCLUSION: Thyroid hormones are necessary for normal growth
and
development since fetal life. Insufficient production or inadequate
activity on
the cellular or molecular level lead to hypothyroidism. These hormones
are
necessary for the development of the brain in the fetus and in the
newborn
infant. Neonatologists and pediatricians deal with child development
issues in
their practice, and many of these issues start during intrauterine
life.
Currently, with neonatal screening, neonatologists and pediatricians
can prevent
irreversible damage through early treatment. They should also be alert
for
dysfunctions such as subclinical hypothyroidism and Hashimoto's
thyroiditis,
which may provoke damage not only to growth, but also to the
neurological and
psychological development of these children and adolescents.
PMID: 18000629 [PubMed - in process]
52: Genet Med. 2007 Nov;9(11):792-6.
Committee Report: advancing the current recommended panel of conditions
for
newborn screening.
Green NS, Rinaldo P, Brower A, Boyle C, Dougherty D, Lloyd-Puryear M,
Mann MY,
Howell RR; Advisory Committee on Heritable Disorders and Genetic
Diseases in
Newborns and Children.
Department of Pediatrics, Columbia University Medical Center, New York,
New York,
USA.
The Advisory Committee on Heritable Disorders and Genetic Diseases in
Newborns
and Children is charged with advising the Secretary of the US
Department of
Health and Human Services in areas relevant to heritable conditions in
children,
especially newborn screening (NBS). This report describes the
formulation by the
Committee of a new process to nominate and review conditions to the
recommended
universal NBS panel. Nominations are currently being solicited.
Committee review
will adhere to the fundamental principles of being transparent,
broadly
accessible, evidence-based and consistent across the process for all of
the
proposed conditions across the process.
PMID: 18007148 [PubMed - in process]
53: Gend Med. 2007 Sep;4(3):248-65.
Implementation of genetics to personalize medicine.
Chung WK.
Division of Molecular Genetics, Columbia University, New York, New York
10032,
USA. [log in to unmask]
BACKGROUND: We stand on the verge of integrating individual genetic and
genomic
information into health care provision and maintenance to improve
health,
increase efficiency, and decrease costs. We are beginning to integrate
information on inherited susceptibility, gene expression, and
predicted
pharmacogenomic response to refine our medical management. OBJECTIVE:
This
article reviews the current utility of genetics and genomics in a wide
array of
clinical circumstances, considers the future applications, and defines
some of
the obstacles and potential solutions to clinical integration of
genomic
medicine. METHODS: Using the search terms genetics, genomics,
pharmacogenomics,
newborn screening, long QT syndrome, BRCA1/BRCA2, maturity onset
diabetes of
youth, diabetes, hemochromatosis, coronary artery disease, copy number
changes,
genetic discrimination, and genetic education, the PubMed database was
searched
from January 2000 to March 2007 to identify pertinent articles. Search
results
were restricted to English-language and human studies. RESULTS: Several
areas of
medicine have begun to incorporate genetics into clinical practice,
including
newborn screening and breast cancer risk stratification and treatment.
Molecular
genetic tests are, and will increasingly become, available for
inherited
arrhythmias, diabetes, cancer, coronary artery disease, and
pharmacogenomics.
However, there are many barriers to implementation, including the cost
of
testing, the genetic literacy of patients and health care providers,
and concerns
about genetic discrimination. CONCLUSION: Genetics and genomics will
be
increasingly utilized in every field of medicine; however, health care
providers
and patients must have realistic expectations about its predictive
power and
current limitations.
PMID: 18022591 [PubMed - in process]
54: Curr Opin Pediatr. 2007 Dec;19(6):700-704.
Duchenne muscular dystrophy: issues in expanding newborn screening.
Kemper AR, Wake MA.
aProgram on Pediatric Health Services Research, Department of
Pediatrics, Duke
University, Durham, North Carolina, USA bCentre for Community Child
Health,
Murdoch Children*s Research Institute and The University of Melbourne,
Royal
Children*s Hospital, Parkville, Victoria, Australia.
PURPOSE OF REVIEW: To illustrate potential risks and benefits of
disease
screening for newborns using the example of Duchenne muscular
dystrophy. RECENT
FINDINGS: There is a wide range in the reported positive predictive
value for
screening male newborns for Duchenne muscular dystrophy by the creatine
kinase
level on dried blood spots. Some parental anxiety is associated with
both early
detection and false-positive screening results. No data are available
about the
impact of the diagnosis on the child, including the impact of early
initiation of
therapy. Studies suggest that few parents change their future
reproductive
planning based on identification of Duchenne muscular dystrophy
through
screening. Few data are available regarding the cost of newborn
screening for
Duchenne muscular dystrophy, and there are insufficient data to
evaluate the
cost-effectiveness of Duchenne muscular dystrophy screening. SUMMARY:
Available
data are insufficient to recommend routine newborn screening for
Duchenne
muscular dystrophy. Understanding the gaps in knowledge provides
insight into the
evidence needed to recommend newborn screening for Duchenne muscular
dystrophy.
Studies are needed to evaluate the potential risks and benefits of
screening,
including the associated incremental costs.
PMID: 18025940 [PubMed - as supplied by publisher]
55: Mol Genet Metab. 2007 Dec;92(4):287-291.
Recommendations for evaluation of responsiveness to tetrahydrobiopterin
(BH(4))
in phenylketonuria and its use in treatment.
Levy H, Burton B, Cederbaum S, Scriver C.
Children*s Hospital Boston and Harvard Medical School, Boston, MA,
United States.
Some individuals with phenylketonuria (PKU) respond to pharmacologic
treatment
with tetrahydrobiopterin (BH(4)) by a reduction in the blood
phenylalanine
concentration. This can result in increased dietary tolerance for
phenylalanine
or, in rare instances, replacement of the phenylalanine-restricted
diet. BH(4) is
now available as sapropterin dihydrochloride under the name KUVAN, a
formulation
of natural BH(4). This commentary contains recommendations for
determining
responsiveness to sapropterin dihydrochloride. The recommendations
include
challenging with an initial daily dose of 20mg/kg and blood
phenylalanine
determinations pre-challenge and on days 1, 7, and 14 with the option
of an
additional continuation to day 28 if required to clarify whether a
response has
occurred. An algorithm depicting this recommendation for the challenge
is
included. The most widely accepted standard of response is 30%
reduction in the
blood phenylalanine concentration, but a lower degree of response might
also be
considered clinically meaningful in some individual circumstances.
Issues include
the potential treatment of those with mild hyperphenylalaninemia who
are not on
diet, challenging neonates who have hyperphenylalaninemia identified by
newborn
screening, and the use of sapropterin dihydrochloride in treatment of
maternal
PKU pregnancies. These recommendations are intended to provide a basis
for the
use of sapropterin dihydrochloride in the treatment of PKU but may be
altered
after close observation of treated patients and carefully performed
research.
PMID: 18036498 [PubMed - as supplied by publisher]
Lori Williamson, MS, CGC, LGC
Co-Director, Master of Science in Genetic Counseling Program
Project Director, Heartland Regional Genetics and Newborn Screening
Collaborative
Clinical Assistant Professor, Pediatrics
University of OK Health Sciences Center
Phone: 405-271-8685 or 405-271-8001 x42180
Fax: 405-271-8697
Address:
OU Children's Hospital
940 NE 13th St., Rm B2418
Oklahoma City, OK 73104
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