Uneventful clinical courses of Korean patients with methylcrotonylglycinuria and their common mutations.
Methylcrotonylglycinuria (MCG) is an inborn error of leucine catabolism and results from the deficiency of 3-methylcrotonyl-CoA carboxylase. Patients with MCG show a highly variable clinical phenotype, ranging from asymptomatic to severe. With the introduction of newborn screening using tandem mass spectrometry, most patients with MCG are identified in their asymptomatic neonatal periods. Owing to their fair clinical outcomes, there exists a controversy over the need for aggressive medical intervention or even for newborn screening for MCG. Our study, reporting 11 Korean MCG patients from nine unrelated families, who were identified by newborn screening or family member testing and normally developed without experiencing an metabolic crisis during the follow-up period of 2.6±1.96 years (range, 1-10 years), indicates that the aggressive medical intervention might not be needed at least for the MCG patients identified by screening program in asymptomatic period. A total of six MCCC2 mutations, but no MCCC1 mutation, were identified in 17 of 18 alleles (94.4%). p.D280Y was identified in the 12/18 alleles (66.7%), indicating a founder effect. Moreover, the rest five variants, p.S342K, p.Q496H, p.P552S, p.T556A and p.P459S, were all previously unreported. The results of our study indicate that the distinct molecular genetic characteristics exist in Korean MCG patients.
Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.
Chang-Woo
CW
Jung
Beom Hee
BH
Lee
Joo Hyun
JH
Kim
Gu-Hwan
GH
Kim
Jin
J
Lee
Jin-Ho
JH
Choi
Han-Wook
HW
Yoo
D044466:Asian People / Q000235:genetics*; D019735:Carbon-Carbon Ligases / Q000172:deficiency / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D005998:Glycine / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation / Q000235:genetics*; D056910:Republic of Korea; D056806:Urea Cycle Disorders, Inborn / Q000235:genetics* / Q000473:pathology*; D014631:Valerates / Q000378:metabolism
D014631:Valerates; C002163:beta-methylcrotonylglycine; D019735:Carbon-Carbon Ligases; D005998:Glycine