[Analysis of clinical features and gene mutations in two Chinese pedigrees with late-onset methylmalonic acidemia, cblC type].
OBJECTIVE
CblC is the most common type of methylmalonic acidemia with homocysteinemia. MMACHC is the coding gene. This study aimed at understanding clinical features and gene mutations in 2 Chinese pedigrees who had late-onset methylmalonic acidemia complicated with homocysteinemia.


METHODS
The clinical data of 2 cases were analyzed. The MMACHC gene mutation was detected using polymerase chain reaction (PCR) and DNA sequencing.


RESULTS
The age of onset was 13 years and 12 years, respectively. They both presented with nervous system symptoms. The main clinical features were developmental retardation and degradation, including motion, speech and intelligence. One patient complained of anemia. The other patient was misdiagnosed as having a viral encephalitis. Both patients showed remarkable elevation of methylmalonic acid and homocysteine levels in urine. Both had received therapy with vitamin B(12). The symptoms were rapidly relieved. The follow-up till now showed apparent improvement in the 2 cases. Three mutations in the MMACHC gene were found in the two Chinese pedigrees. Both patients were compound heterozygotes of two mutant alleles: one patient had a G-to-A transition at nucleotide 482 (G482A) that caused an arginine-to-glutamine substitution at position 161 of the protein (R161Q), and a deletion of AAG at nucleotide 658_660 (658_660delAAG) which resulted in lysine deleting at position 220 of the protein (K220del); the other patient had a G482A and a G-to-A transition at nucleotide 609 (G609A) that caused a tryptophan-to-termination codon substitution at position 203 of the protein (W203X). Otherwise, the authors also detected parents of two families. Each had a heterozygote of one mutation.


CONCLUSIONS
Late-onset methylmalonic acidemia patients had a variety of clinical manifestation, the first symptom was mainly abnormality of nervous system. One case was accompanied with hematological abnormalities. Two patients were vitamin B(12) responsive. In this study, the mutations were all detected on the fourth exon, the G482A mutation was probably associated with late-onset cases.
Institute for Pediatric Research, Shenzhen Children's Hospital, Shenzhen 518026, China.
Dong
D
Cui
Shu-li
SL
Chen
Peng-qiang
PQ
Wen
Yu-hui
YH
Hu
Xiao-wen
XW
Chen
Dan
D
Shen
Quan
Q
Yuan
Ping
P
Song
Jian-xiang
JX
Liao
Cheng-rong
CR
Li
D000293:Adolescent; D000592:Amino Acid Metabolism, Inborn Errors / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D005260:Female; D006801:Humans; D008764:Methylmalonic Acid / Q000097:blood*; D009154:Mutation; D010088:Oxidoreductases; D010375:Pedigree; D014805:Vitamin B 12
D002352:Carrier Proteins; D008764:Methylmalonic Acid; C508359:MMACHC protein, human; D010088:Oxidoreductases; D014805:Vitamin B 12