Abstract:
Multiple carboxylase deficiency (MCD) is a rare autosomal recessive disorder of biotin-responsive carboxylases. There are two genetically distinct causes, mutations in HLCS or BTD. In Thailand, there have been no previous reports of biochemical and molecular characteristics of Thai patients. In this study, we have demonstrated biotinidase activity in the plasma using colorimetric assay of four patients and 245 normal controls. The mean control activity was 5.63+-1.25 nmol/min/ml. All 4 patients had normal biotinidase activity. Mutation analysis is perfomed by direct sequencing all coding region of the HLCS having 11 exons and 2178 bp coding region and confirmation by restriction enzyme digestion. The results show that two patients were homozygous for the common R508W mutation and the other two were compoundly heterozygous for R508W/G505R and R508W/mutation-not-found. The G505R has not been previously reported. The R508W was present in 6 of 8 alleles found in four patients. To determine the origin of these mutations, we determined microsatellite markers in the HLCS and found that R508W was present in three haplotypes. In conclusion, we developed and determined biotinidase activity in Thais for the first time and found a novel mutation. In addition, our results suggest that the R508W could make diagnosis of MCD in aLL Thai patients, making diagnose of the disease faster and having genetic counseling implication.
