Clinical, biochemical and genetic analysis of a Chinese Han pedigree with holocarboxylase synthetase deficiency: a case report

Abstract Background: Holocarboxylase synthetase (HLCS) deficiency is a rare inborn disorder of biotin metabolism, which results in the defect of several biotin-dependent carboxylases and presents with metabolic ketoacidosis and skin lesions. Case presentation : In this study, we have reported a Chinese Han pedigree with HLCS deficiency diagnosed using next-generation sequencing and validated with Sanger sequencing of HLCS and BTD gene. The Chinese proband carries a common missense mutation c.1522C>T (p.Arg508Trp) in exon 9 of HLCS gene, which generates an increased K m for biotin. A novel frameshift mutation c.1006_1007delGA (p.Glu336Thrfs*15) in exon 6 of H L CS gene produces a low Vmax and is predicted to be deleterious through PROVEAN and MutationTaster. A novel heterozygous mutation c.638_642delAACAC (p.His213Profs*4) in BTD gene is also identified. Otherwise, the proband presents abnormal BAEP suggesting hearing damage in the acute episode. Conclusions: A Chinese proband carries a reported Arg508Trp variant, a novel 2-bp frameshift mutation c.1006_1007delGA (p.Glu336Thr) expanding mutational spectrum of HLCS gene, and a novel heterozygous mutation c.638_642delAACAC (p.His213Profs*4) expanding mutational spectrum of BTD gene. Furthermore, the reversible hearing damage is rarely reported in the patients with HLCS deficiency, which deserves for further discussion.