PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 16571691

Newborn screening: complexities in universal genetic testing.

Nancy S Green·Siobhan M Dolan·Thomas H Murray
View original source ↗Export metadata ↓

Abstract

Newborn screening (NBS)--in which each newborn infant is screened for up to 50 specific metabolic disorders for early detection and intervention--is the first program of populationwide genetic testing. As a public health intervention, NBS has greatly improved the lives of thousands of affected children. New technologies and new economic and social forces pose significant ethical and clinical challenges to NBS. Two primary challenges concern (1) accommodating clinical and ethical standards to rapid technological developments in NBS and (2) preparing public health systems to respond to the medical advances and social forces driving expansion of NBS programs. We describe and analyze these challenges through consideration of 3 disorders: phenylketonuria, medium-chain acyl-CoA dehydrogenase deficiency, and cystic fibrosis.

Explore related subjects

Acyl-CoA DehydrogenaseAdrenal Hyperplasia, CongenitalCultural DiversityCystic FibrosisEarly DiagnosisGenetic TestingHumansInfant, NewbornMandatory TestingMetabolism, Inborn ErrorsNeonatal ScreeningPhenylketonuriasPoliticsPublic Health AdministrationSocial JusticeJournal ArticleResearch Support, N.I.H., Extramural

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Nancy S Green, Siobhan M Dolan, Thomas H Murray. 2006-03-29. Newborn screening: complexities in universal genetic testing.. https://doi.org/10.2105/ajph.2005.070300

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2007

Outcome of neonatal screening for medium-chain acyl-CoA dehydrogenase deficiency in Australia: a cohort study.

BACKGROUND: Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is the disorder thought most to justify neonatal screening by tandem-mass spectrometry because, without screening, there seems to be substantial morbidity and mortality. Our aim was to assess the overall effectiveness of neonatal screening for MCAD deficiency in Australia. METHODS: We identified MCAD-deficient patients from a total population of 2,495,000 Australian neonates (810,000 screened) born between April 1, 1994, and March 31, 2004. Those from a cohort of 1,995,000 (460,000 screened) were followed up for at least 4 years, and we recorded number of deaths and severe episodes, medical and neuropsychological outcome, and hospital admissions within the screened and unscreened groups. FINDINGS: In cohorts aged at least 4 years there were 35 MCAD-deficient patients in those not screened (2.28 per 100,000 total population) and 24 in the screened population (5.2 per 100,000). We estimated that patients with this disorder in the unscreened cohort remained undiagnosed. Before 4 years of age, three screened patients had an episode of severe decompensation (including one neonatal death) versus 23 unscreened patients (including five deaths). At the most conservative estimate, relative risk of an adverse event was 0.44 (95% CI 0.13-1.45). In the larger cohort the relative risk (screened vs unscreened) of an adverse event by age 2 years was 0.26 (95% CI 0.07-0.97), also a conservative estimate. 38 of 52 living patients had neuropsychological testing, with no suggestions of significant differences in general cognitive outcome between the groups. INTERPRETATION: Screening is effective in patients with MCAD deficiency since early diagnosis reduces deaths and severe adverse events in children up to the age of 4 years.

Acyl-CoA Dehydrogenase↗
PubMed2006

Acute liver failure in pregnancy associated with maternal MCAD deficiency.

In recent years the association between severe pregnancy complications and fetal fatty acid oxidation (FAO) disorders has been reported. However, there are few descriptions of a maternal FAO disorder leading to these complications. We describe acute liver failure associated with an undiagnosed maternal medium-chain acyl-CoA dehydrogenase (MCAD) deficiency. The previously healthy proband presented at the 39th week with an itchy rash, palmar erythema and trace proteinuria; she was admitted onto a maternity ward. Acute fatty liver was suspected from the blood tests and a Caesarean section was performed, delivering a healthy boy. Cord blood samples were taken at delivery as part of an ongoing research project. The analysis of the cord blood sample showed a high concentration of octanoylcarnitine of 2.3 micromol/L (reference <0.1), suggesting a possible fatty acid oxidation disorder. However, subsequent acylcarnitine analyses of the baby's blood showed a normal pattern. The proband was further evaluated by urine organic acids and acylcarnitine profile. Elevated concentrations of hexanoylglycine in urine and octanoylcarnitine in blood spots were found, consistent with a diagnosis of MCAD deficiency. Mutation analyses confirmed that she was homozygous for c.985A>G (K329E). Even though these pregnancy complications are rare and it is not possible to affirm that the proband's acute liver failure was secondary to an undiagnosed MCAD deficiency, it seems likely.

Acyl-CoA Dehydrogenase↗