Holocarboxylase synthetase deficiency induced by HLCS gene mutations: a rare disease study / 中国当代儿科杂志

A boy, aged 16 months, attended the hospital due to head and facial erythema for 15 months and vulva erythema for 10 months with aggravation for 5 days. The boy developed perioral and periocular erythema in the neonatal period and had erythema and papules with desquamation and erosion in the neck, armpit, and trigone of vulva in infancy. Blood gas analysis showed metabolic acidosis; the analysis of amino acid and acylcarnitine profiles for inherited metabolic diseases and the analysis of organic acid in urine suggested multiple carboxylase deficiency; genetic testing showed a homozygous mutation of c.1522C>T(p.R508W) in the HLCS gene. Finally the boy was diagnosed with holocarboxylase synthetase deficiency and achieved a good clinical outcome after oral biotin treatment. This article analyzes the clinical data of a child with holocarboxylase synthetase deficiency and summarizes the etiology, diagnosis, and treatment of this child, so as to provide ideas for clinicians to diagnose this rare disease.

Expert consensus on screening, diagnosis and treatment of multiple carboxylase deficiency / 浙江大学学报·医学版

Multiple carboxylase deficiency (MCD) includes autosomal recessive holocarboxylase synthetase (HLCS) deficiency and biotinidase (BTD) deficiency, which are caused by and gene mutations respectively. Neonatal screening for HLCS deficiency is based on 3-hydroxyisovaleryl carnitine in dry blood filter paper, and BTD deficiency is based on BTD activity determination. HLCS deficiency and BTD deficiency are characterized by neurocutaneous syndrome and organic aciduria, however, they are different in onset age, neurological symptoms and metabolic decompensation, which needed to be differentiated from acquired biotin deficiency or other genetic metabolic diseases. The diagnosis of the disease requires a combination of biochemical characteristics of hematuria, enzyme activity determination and genetic test. Routine biotin doses are effective for most MCD patients. This consensus is intended to benefit early screening and diagnosis of MCD.

The clinical and genetic features of holocarboxylase synthetase deficiency in a male patient / 临床儿科杂志

Objective To investigate the clinical, biochemical and genetic features of a Chinese boy with holocarboxylase synthetase deficiency (HCSD). Methods The clinical and genetic data of a rare case of HCSD were retrospectively analyzed. Results After birth, the boy showed development delay. At 3 months old, the boy was started with rehabilitation. Tandem mass spectrum and gas chromatography analysis was carried in the 5th month after birth because of the recurrent upper respiratory tract infection and elevated level of C5-OH in the blood and decreased level of C0,and elevated level of 3-OH-propionic, pyruvic acid, methylcrotonylglycine in the urine were in accordance with the HCSD. Genetic analysis found compound heterozygous mutations of c.1648G>A and c.1544G>A in gene, of which the latter one is novel. After the treatment of biotin (20 mg/d) and L-Carnitine, the condition of this boy was gradually improved. Conclutions HCSD is characterized with slow onset and inconspicuous manifestations. The confirmed diagnosis can be built with MS/MS, GC/MS analysis and gene mutation analysis. The effect of early biotin treatment is satisfactory. In this study,we carried out clinical and genetic diagnosis,which lays a solid foundation for prenatal diagnosis and early treatment.