WUH-LIANG HWUSuzuki Y.Yang X.Li X.Chou S.-P.Narisawa K.WEN-YU TSAI2020-12-162020-12-1620000929-6646https://www.scopus.com/inward/record.uri?eid=2-s2.0-0034030910&partnerID=40&md5=52086205f8ab4c5443e3c2eda26d5b5ahttps://scholars.lib.ntu.edu.tw/handle/123456789/526081Holocarboxylase synthetase (HCS) is responsible for the biotinylation of pyruvate carboxylase, propionyl coenzyme A (CoA) carboxylase, β- methylcrotonoyl CoA carboxylase, and acetyl CoA carboxylase. We report on a patient with HCS deficiency resulting in a rare metabolic disease. The patient, a 2-year-old boy, presented with vomiting, consciousness disturbance, and dyspnea. Laboratory, examinations showed hyperglycemia, hyperammonemia, lactic acidosis, and excretion of large amounts of β- hydroxyisovalerate and β-methylcrotonylglycine in the urine. After 10 days of treatment with biotin 5 mg · kg-1 · day-1, the abnormal organic acids in his urine had almost completely disappeared. There were no subsequent attacks, and his growth and development remained normal during 1 year of follow- up. Nucleotide sequence analysis of the HCS cDNA of the patient revealed a homozygous 1809C→T (R508W) mutation. The R508W mutation is found worldwide, and might be associated with higher residual HCS activity than other mutations. Late-onset HCS deficiency cannot be differentiated clinically from biotinidase deficiency. Prompt and correct diagnosis is important for these biotin- responsive disorders.Biotin; Holocarboxylase synthetase; Multiple carboxylase deficiency; R508W mutation[SDGs]SDG3biotinidase; article; case report; chemical analysis; consciousness disorder; disorders of carbohydrate metabolism; dyspnea; enzyme deficiency; gene mutation; human; male; preschool child; sequence analysis; vomiting; Carbon-Nitrogen Ligases; Child, Preschool; Humans; Male; Mutationjournal article107700352-s2.0-0034030910