Suormala T, Fowler B, Jakobs C, Duran M, Lehnert W, Raab K, Wick H, Baumgartner E R
University Children's Hospital, Basel, Switzerland.
Eur J Pediatr. 1998 Jul;157(7):570-5. doi: 10.1007/s004310050881.
The clinical and biochemical findings in a family with late-onset holocarboxylase synthetase (HCS) deficiency are described. The index patient had two life-threatening episodes of metabolic decompensation at the age of 13 and 18 months with ketotic hypoglycaemia, vomiting and progressive loss of consciousness. The child recovered without biotin therapy. Organic aciduria characteristic of multiple carboxylase deficiency (MCD) was found, however, the key metabolites were only slightly elevated in some samples. Biotinidase deficiency was considered but excluded by the finding of normal plasma biotinidase activity. The correct diagnosis was made only at the age of 19 months when severe MCD was found in lymphocytes in the presence of normal plasma biotin concentration. HCS deficiency was confirmed by fibroblast studies. Biotin therapy (20 or 40 mg/day) prevented further episodes and normalized biochemical parameters with so far normal development. During two subsequent pregnancies, 10 mg biotin/day was administered to the mother from the 20th week of gestation. At delivery plasma biotin in cord blood samples was 3 4 times higher than in maternal plasma. The 2nd child was unaffected. In the 3rd pregnancy prenatal diagnosis was performed at 16 weeks of gestation. The concentration of methylcitrate in amniotic fluid was within the normal range and that of 3-hydroxyisovalerate only slightly elevated. However, enzyme assays in cultured amniotic fluid cells were consistent with an affected fetus. At birth, carboxylase activities in lymphocytes of this newborn were only moderately decreased to 37% of mean normal. HCS deficiency was confirmed postnatally in fibroblasts. Development remains normal on biotin therapy (20 mg/day).
Prenatal diagnosis in families with milder forms of HCS deficiency has to be performed by enzyme assays in cultured amniotic cells since organic acid analysis of amniotic fluid may be inconclusive in affected fetuses. Biotin administered prenatally is effectively taken up by the fetus and prevents functional deficiency of the carboxylases in an affected newborn.
本文描述了一个患有迟发性全羧化酶合成酶（HCS）缺乏症家庭的临床和生化检查结果。索引患者在13个月和18个月大时发生了两次危及生命的代谢失代偿发作，伴有酮症性低血糖、呕吐和意识逐渐丧失。该患儿未经生物素治疗便康复了。发现了多种羧化酶缺乏症（MCD）特有的有机酸尿症，然而，关键代谢物在某些样本中仅略有升高。考虑过生物素酶缺乏症，但血浆生物素酶活性正常的结果排除了这种可能性。直到19个月大时才做出正确诊断，当时在血浆生物素浓度正常的情况下，淋巴细胞中发现了严重的MCD。通过成纤维细胞研究证实了HCS缺乏症。生物素治疗（20或40毫克/天）预防了进一步发作，并使生化参数恢复正常，到目前为止发育正常。在随后的两次怀孕期间，从妊娠第20周起，母亲每天服用10毫克生物素。分娩时，脐带血样本中的血浆生物素比母体血浆高3至4倍。第二个孩子未受影响。在第三次怀孕期间，在妊娠16周时进行了产前诊断。羊水柠檬酸浓度在正常范围内，3 - 羟基异戊酸浓度仅略有升高。然而，培养的羊水细胞中的酶分析结果与受影响的胎儿一致。出生时，这名新生儿淋巴细胞中的羧化酶活性仅中度降低至正常平均值的37%。出生后在成纤维细胞中证实了HCS缺乏症。在生物素治疗（20毫克/天）下发育仍正常。
对于患有较轻形式HCS缺乏症的家庭，产前诊断必须通过培养的羊水细胞中的酶分析来进行，因为羊水的有机酸分析对于受影响的胎儿可能没有定论。产前给予的生物素能被胎儿有效吸收，并预防受影响新生儿羧化酶的功能缺陷。
