Hwu W L, Suzuki Y, Yang X, Li X, Chou S P, Narisawa K, Tsai W Y
Department of Pediatrics and Medical Genetics, College of Medicine, National Taiwan University, Taipei.
J Formos Med Assoc. 2000 Feb;99(2):174-7.
Holocarboxylase synthetase (HCS) is responsible for the biotinylation of pyruvate carboxylase, propionyl coenzyme A (CoA) carboxylase, beta-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 beta-hydroxyisovalerate and beta-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.
全羧化酶合成酶（HCS）负责丙酮酸羧化酶、丙酰辅酶A（CoA）羧化酶、β-甲基巴豆酰CoA羧化酶和乙酰CoA羧化酶的生物素化。我们报告了一名患有HCS缺乏症的患者，该疾病导致一种罕见的代谢性疾病。该患者为一名2岁男孩，出现呕吐、意识障碍和呼吸困难。实验室检查显示高血糖、高氨血症、乳酸酸中毒，尿液中大量排出β-羟基异戊酸和β-甲基巴豆酰甘氨酸。在以5mg·kg-1·天-1的生物素治疗10天后，他尿液中的异常有机酸几乎完全消失。后续未再发作，在1年的随访期间其生长发育保持正常。对该患者HCS cDNA的核苷酸序列分析显示存在纯合的1809C→T（R508W）突变。R508W突变在全球范围内均有发现，可能比其他突变与更高的HCS残余活性相关。迟发性HCS缺乏症在临床上无法与生物素酶缺乏症相鉴别。对于这些生物素反应性疾病，及时且正确的诊断很重要。
