Molecular and functional characterisation of mild MCAD deficiency.
We report a novel mild variant of medium-chain acyl-CoA dehydrogenase deficiency (MCADD) diagnosed in four infants who, in neonatal screening, showed abnormal acylcarnitine profiles indicative of MCADD. Three patients showed completely normal urinary organic acids and phenylpropionic acid loading tests were normal in all four patients. Enzyme studies showed residual MCAD activities between "classical" MCADD and heterozygotes. ACADM gene analysis revealed compound heterozygosity for the common mutation K329E and a novel mutation, Y67H, in two cases, and homozygosity for mutation G267R and the novel mutation S245L, respectively, in two children of consanguineous parents. As in other metabolic disorders, the distinction between "normal" and "disease" in MCAD deficiency is blurring into a spectrum of enzyme deficiency states caused by different mutations in the ACADM gene potentially influenced by factors affecting intracellular protein processing.
Zschocke
J
J
Division of Metabolic and Endocrine Diseases, University Children's Hospital, Heidelberg, Germany. johannes_zschocke@med.uni-heidelberg.de
Schulze
A
A
Lindner
M
M
Fiesel
S
S
Olgemöller
K
K
Hoffmann
G F
GF
Penzien
J
J
Ruiter
J P
JP
Wanders
R J
RJ
Mayatepek
E
E
D042964:Acyl-CoA Dehydrogenase; D044944:Acyl-CoA Dehydrogenases / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D002331:Carnitine / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005260:Female; D005347:Fibroblasts; D014644:Genetic Variation / Q000235:genetics; D005858:Germany; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007223:Infant; D008214:Lymphocytes / Q000201:enzymology; D008297:Male; D009154:Mutation / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics; D010666:Phenylpropionates / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000235:genetics; D014421:Turkey
D010666:Phenylpropionates; C116917:acylcarnitine; D044944:Acyl-CoA Dehydrogenases; D042964:Acyl-CoA Dehydrogenase; D002331:Carnitine