To investigate the clinical and genetic characteristics of holocarboxylase synthetase deficiency (HCSD) in a case.

Clinical data of a child diagnosed with HCSD in Qilu Children's Hospital of Shandong University in August 2014 was retrospectively studied. The informed consent of the patient’s parents was obtained and the local ethical committee approval had been received. The child patient was female, 1 year and 6 months old. She was admitted to hospital because of vomiting along with diarrhea for 3 days and fever for 2 days. Her mental reaction was poor, and she had metabolic acidosis, but the treatment effect of correcting acidosis was poor. Urine organic acid test showed that the levels of 3-hydroxy isovaleric acid, 3-hydroxypropionic acid, 3-methyl crotonic acyl glycine, lactic acid and pyruvate in this child were higher than those in normal child. Mutations in holocarboxylase synthetase (HLCS) gene were detected using the second generation sequencing technology and then verified by Sanger.

The second generation sequencing and Sanger verification showed that two heterozygous mutations, c.1080A>C and c.782delG, were found in exons of the HLCS gene in this child. c.1080A>C leads to amino acid change, that is p.R360S; and c.782delG leads to amino acid frameshift. The child patient's genetic mutations were inherited from her parents, c.1080A>C from her father and c.782delG from her mother. The clinical symptoms disappeared after targeted treatments.

HCSD lacks of specificity in clinical manifestations. The second generation and Sanger sequencing techniques can reveal HLCS gene mutations in child patient and then confirmed HCSD at the gene level.