Lack of genotype-phenotype correlations and outcome in MCAD deficiency diagnosed by newborn screening in New York State.

摘要: Abstract Introduction: Medium chain acyl-CoA dehydrogenase (MCAD) deficiency is one of the most common inborn errors metabolism. Affected patients have impaired ability to break down medium fatty acids during fasting, and typically present in early years life with hypoketotic hypoglycemia, Reye syndrome-like symptoms, brain damage or death. The development newborn screening (NBS) for MCAD has greatly improved outcome, but some still appear at risk severe complications. We reviewed outcome identified by New York State NBS process identify biochemical genotypic markers which might predict outcome. Method: All eight follow-up centers contributed cases diagnosed screen, who received diagnostic care their clinic. Data included gender, age, birthweight, initial octanoylcarnitine level (C8) C8/C2 ratio, C8 hexanoylglycine, race/ethnicity, presence neonatal later symptoms. Results: 53 deficiency. More than quarter had a post-neonatal symptomatic admission (predominantly lethargy associated an intercurrent illness). No genotype was protective There relationship between ratio occurrence symptoms (7.3μmol/L asymptomatic vs. 19.1μmol/L symptomatic, p 30μmol/L; these infants high rate multiple episodes history sibling death from "SIDS", deletion, nonsense splice sites mutations. Infants having episode were more likely higher on predicted strongly affect protein function. In our ethnically diverse group patients, c.985A>G mutation rarely found non-Caucasians. Discussion: metabolite profile strong suggests that least neonates levels may be demonstrating increased susceptibility catabolic stress, merit additional precautions. Our data also suggest are carry mutations including homozygosity mutation, deletions, site reports significant hypoglycemia illness over even when medical intervention recommended (and not profoundly elevated) underscores importance continued vigilance prevent stressful fasting this disorder.