Affordable Access

Publisher Website

Molecular analysis of Taiwanese patients with 3-Hydroxy-3-methylglutaryl CoA lyase deficiency

Clinica Chimica Acta
Publication Date
DOI: 10.1016/j.cca.2008.11.004
  • 3-Hydroxy-3-Methylglutaryl Coa Lyase
  • 3-Hydroxy-3-Methylglutaryl Coa Lyase Deficiency
  • Hl Deficiency
  • Gene Mutation
  • Biology
  • Medicine


Abstract Background 3-Hydroxy-3-methylglutaryl CoA lyase deficiency (HL deficiency) is a rare autosomal recessive mitochondrial disease characterized by a deficiency in the enzyme 3-Hydroxy-3-methylglutaryl CoA lyase (HMGCL). Here, we report on novel mutations identified in the HMGCL gene in 2 Taiwanese patients with HL deficiency. Methods Analysis of organic acids in urine was performed using gas chromatography-mass spectrometry to confirm HL deficiency in the two subjects. The mutations in their HMGCL genes then were determined by direct sequencing. In addition, the effect of a splice site mutation was determined using reverse transcription-polymerase chain reactions (RT-PCR). Results A total of 3 novel mutations in the HMGCL gene were revealed by molecular analysis: one missense mutation (c.494G > T, p.Arg165Gln) and 2 splice site mutations (IVS3 + 1G > A, IVS6-1G > A). The results of RT-PCR revealed that an IVS3 + 1G > A mutation leads to skipping of exon3. We also calculated that the incidence of HL deficiency in Taiwan is < 1 per 1,000,000 live births. Conclusions The results of this study suggest that unique HMGCL gene mutations exist in Taiwanese HL deficiency patients. Therefore, HMGCL gene profiling may be useful in genetic counseling for families affected by HL deficiency.

There are no comments yet on this publication. Be the first to share your thoughts.