Novel mutations causing medium chain acyl-CoA dehydrogenase deficiency: under-representation of the common c.985 A > G mutation in the New York state population.

Novel mutations causing medium chain acyl-CoA dehydrogenase deficiency: under-representation of the common c.985 A > G mutation in the New York state population.

MedLine Citation:	PMID: 18241067 Owner: NLM Status: MEDLINE
Abstract/OtherAbstract:	Medium chain acyl-CoA dehydrogenase deficiency (MCADD) is one of the most common fatty acid oxidation disorders. A subpopulation of children with MCADD present with metabolic crisis induced by fasting or illness, become lethargic, and can experience seizures or coma, culminating in a 20% mortality rate during the first episode. The frequency of these metabolic crises can be reduced with early diagnosis and treatment. The prevalence of MCADD in the United States is estimated to be 1 per 15,000 with p.K304E (c.985A > G) accounting for 90% of mutant alleles. In an 18-month period after initiating screening, the New York State Newborn Screening Mass Spectrometry Laboratory screened 385,893 newborns and referred 511 samples with elevated (>or=0.3 micromol/L) octanoylcarnitine (C8) levels for molecular testing. Of these referrals, six p.K304E homozygotes and 154 heterozygotes were identified. Twenty infants were biochemically confirmed with MCADD, per report from the child's pediatrician and/or treatment center. In these 20 cases, p.K304E accounted for only 47.5% of the mutant alleles. Further testing showed a second variant, p.Y42H, accounted for 7.5% of mutant alleles while the remaining 45% were unknown. Samples from all diagnosed non-p.K304E homozygous infants, and samples with C8 levels >or=1.0 micromol/L were sequenced (n = 16). Six novel and seven previously reported mutations were detected. These results suggest that p.K304E has a far lower representation in New York newborns with MCADD than current literature estimates and its full mutational spectrum is still unknown.

Authors:	Matthew J Nichols; Carlos A Saavedra-Matiz; Kenneth A Pass; Michele Caggana
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Publication Detail:	Type: Journal Article; Research Support, Non-U.S. Gov't
Journal Detail:	Title: American journal of medical genetics. Part A Volume: 146A ISSN: 1552-4833 ISO Abbreviation: Am. J. Med. Genet. A Publication Date: 2008 Mar
Date Detail:	Created Date: 2008-02-28 Completed Date: 2008-05-07 Revised Date: 2009-11-19
Medline Journal Info:	Nlm Unique ID: 101235741 Medline TA: Am J Med Genet A Country: United States
Other Details:	Languages: eng Pagination: 610-9 Citation Subset: IM
Copyright Information:	(c) 2008 Wiley-Liss, Inc.
Affiliation:	Division of Genetic Disorders, Newborn Screening Program, Wadsworth Center, New York State Department of Health, Albany, New York 12201, USA.
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MeSH Terms
Descriptor/Qualifier:	Acyl-CoA Dehydrogenase / deficiency, genetics Base Sequence Deficiency Diseases / diagnosis, epidemiology Genetic Testing Humans Infant, Newborn Molecular Sequence Data Neonatal Screening New York / epidemiology Point Mutation* Population Sequence Analysis, DNA United States
Chemical
Reg. No./Substance:	EC 1.3.99.3/Acyl-CoA Dehydrogenase

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