Biochemical and molecular analyses in three patients with 3-hydroxy-3-methylglutaric aciduria

Two methods, spectrophotometry and HPLC, were compared in the analyses of 3-hydroxy-3-methylglutaryl-CoA lyase (HL) activity in three unrelated Czech patients with 3-hydroxy-3-methylglutaric (HMG) aciduria and their family members. The HL activities in cultured fibroblasts and/or isolated lymphocytes of probands were below the detection limits of the methods used. Both methods were also suitable for recognition of all heterozygotes in affected families. We searched for pathogenic mutations in the HL gene. Molecular analyses revealed that two patients are homozygous for known mutation H233R and R41Q, respectively, whereas the third patient is a compound heterozygote for the mutation H233R and a novel mutation Pro9fs(-1). This study expands the knowledge of the genotypic variability of the HMG aciduria.