title: Phenotypic and mutation spectrums of Thai patients with isovaleric acidemia.
abstract: BACKGROUND
  Isovaleric acidemia (IVA) is an autosomal recessive disorder caused by deficiency of isovaleryl-CoA dehydrogenase (IVD). Clinical features include vomiting, lethargy, metabolic acidosis, and "sweaty feet" odor. The pathognomonic metabolite, isovalerylglycine, is detected on urine organic acid analysis. Clinical diagnosis of IVA can be confirmed on mutation analysis of the IVD gene.
  
  
  METHODS
  The cases of five unrelated Thai patients with IVA, identified on urine organic acid analysis, are described. Mutation analysis of the IVD gene was performed using polymerase chain reaction sequencing of the entire coding regions.
  
  
  RESULTS
  Four out of the five IVA patients had an acute neonatal form. The hematologic abnormalities were common and thus could be presenting symptoms in the absence of metabolic acidosis. As for the neurological outcome, only one patient had normal intelligence. Mutation analysis of the IVD gene identified the mutations c.457-3_2CA>GG, c.1199A>G (p.Y371C), c.281C>G (p.A65G), c.358G>A (p.G91R), and c.827T>C (p.L247P). The poor outcome in most patients might be explained by the delayed diagnosis and initial unavailability of the metabolic formulas and medications in Thailand. The c.457-3_2CA>GG mutation was identified in all of the present patients. This suggests that it is the most common mutation in the Thai population. Therefore, it could be a founder mutation in Thai subjects. One of the present Thai IVA patients also had the p.Y371C mutation, which is common in Han Chinese subjects. In addition, two novel mutations, p.A65G and p.L247P, were identified.
  
  
  CONCLUSIONS
  The present study provides additional knowledge on the genotype-phenotype of IVA, suggesting that IVD mutations in Asian populations are distinct from these in Western populations.
authors: Division of Medical Genetics, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. nithiwat_v@hotmail.com
authors: Nithiwat
authors: N
authors: Vatanavicharn
authors: Somporn
authors: S
authors: Liammongkolkul
authors: Osamu
authors: O
authors: Sakamoto
authors: Achara
authors: A
authors: Sathienkijkanchai
authors: Pornswan
authors: P
authors: Wasant
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000201:enzymology / Q000208:ethnology / Q000235:genetics*; D044466:Asian People; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007231:Infant, Newborn; D050769:Isovaleryl-CoA Dehydrogenase / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D008297:Male; D009154:Mutation; D010641:Phenotype; D013785:Thailand
chemical_list: D004247:DNA; D050769:Isovaleryl-CoA Dehydrogenase