Genotypic differences of MCAD deficiency in the Asian population: novel genotype and clinical symptoms preceding newborn screening notification.
OBJECTIVE
In contrast to its high prevalence in Caucasians, medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is reported to be an extremely rare metabolic disorder in the Asian population. The common MCAD gene (ACADM) mutation 985A>G (p.K329E), accounting for the majority of cases in Caucasians, has not been detected in this ethnic group, and the spectrum of ACADM mutations has remained unknown.


METHODS
Biochemical genetic testing including plasma acylcarnitine and urine acylglycine analyses, as well as sequencing of ACADM was performed in a Korean family with a newborn who had an elevated octanoyl (C8) carnitine concentration by newborn screening (NBS). Genotyping of 50 Korean newborns with normal NBS results was performed.


RESULTS
We report the identification of the first Korean patient with MCAD deficiency, caused by a novel missense mutation in ACADM, 843A>T (R281S), and a 4-bp deletion, c.449_452delCTGA. The patient became symptomatic before notification of the abnormal NBS result. Both the father and a brother who were identified as carriers for the 4-bp deletion had mildly elevated plasma C8 and C10:1 carnitine concentrations, whereas the acylcarnitine profile was normal in the mother who carries the missense mutation.


CONCLUSIONS
The 4-bp deletion may represent a common Asian ACADM mutation, considering that it recently has also been found in two of the three Japanese patients in whom genotyping was performed. Greater availability of MCAD mutation analysis is likely to unravel the molecular basis of MCAD deficiency in the Asian population that might differ from Caucasians.
Ensenauer
Regina
R
Biochemical Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
Winters
Jennifer L
JL
Parton
Patricia A
PA
Kronn
David F
DF
Kim
Jong-Won
JW
Matern
Dietrich
D
Rinaldo
Piero
P
Hahn
Si Houn
SH
D042964:Acyl-CoA Dehydrogenase / Q000172:deficiency* / Q000235:genetics*; D001483:Base Sequence; D002331:Carnitine / Q000031:analogs & derivatives / Q000097:blood; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D007723:Korea / Q000208:ethnology; D008297:Male; D008661:Metabolism, Inborn Errors / Q000453:epidemiology / Q000208:ethnology* / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics; D015997:Neonatal Screening / Q000379:methods*; D009518:New York / Q000453:epidemiology; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion / Q000235:genetics
C116917:acylcarnitine; D042964:Acyl-CoA Dehydrogenase; C008698:octanoylcarnitine; D002331:Carnitine