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

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