Medium-chain acyl-CoA dehydrogenase deficiency : Genotype-biochemical phenotype correlations

摘要: Abstract The fatty acid oxidation disorder most commonly identified by tandem mass spectrometry newborn screening is the potentially fatal medium-chain acyl-CoA dehydrogenase deficiency (MCAD). In clinically presenting cases, 80% are homozygous for common mutation, c.985A > G and 18% heterozygous. We screened 592,785 babies 34 with MCAD, 17 c.985A > G, 14 one copy, 3 no copy. sequenced exons of 19 patients, carrying or copy two marginal findings, examined correlations between groups mutations biochemical markers. found known putative pathogenic in 18 patients. Two appeared more than once: c.199T > C, not recorded cases ( n  = 4), c.583G > A  = 2). Patients had highest levels neonatal octanoylcarnitine, plasma octanoylcarnitine when asymptomatic, urinary acylglycines. Compound heterozygotes other intermediate levels, those without heterozygous that c.199T > C lowest these analytes. There was overlap all values. appear to have functional effects towards severe end spectrum, mutation a smaller effect, as has been previously postulated. If results confirmed extended, this could influence advice given parents MCAD detected screening, make management specific. meantime, patients have, definition, defect require careful clinical management.