生物素酶缺乏症的诊断与治疗六例分析  

Diagnosis and treatment of biotinidase deficiency-clinical study of six patients

作　　者：杨艳玲[1] 山口清次 田上泰子 张月华[1] 熊晖[1] 长谷川有纪 木村正彦 花井润师 藤田晃三 钱宁[1] 何晓菊[1] 吴晔[1] 包新华[1] 秦炯[1] 吴希如[1] 

机构地区：[1]北京大学第一医院儿科,100034 [2]日本岛根医科大学小儿科 [3]日本札幌市卫生研究所

出　　处：《中华儿科杂志》2003年第4期249-251,共3页Chinese Journal of Pediatrics

基　　金：卫生部临床学科重点项目资助 ( 2 0 0 1 0 3)

摘　　要：目的　探讨生物素酶缺乏症的临床特征、诊断与治疗方法。方法　运用尿有机酸分析(气相色谱 质谱联用 )及干燥滤纸血片生物素酶测定进行筛查与诊断 ,对 6例生物素酶缺乏症患儿的临床经过进行分析。结果　 (1 ) 6例干燥滤纸血片生物素酶活性均小于 0 .1pmol/ (min·3mm)。尿有机酸分析显示例 1、2、3、5乳酸、3 羟基丙酸、丙酮酸、丙酰甘氨酸、甲基巴豆酰甘氨酸、β 羟基异戊酸浓度明显增高 ,例 4、6仅显示乳酸、丙酮酸、甲基巴豆酰甘氨酸增高。 (2 ) 6例各有不同程度的神经系统损害和皮肤粘膜异常。例 1～ 3为婴儿期起病 ,因惊厥、智力运动倒退、呕吐、意识障碍来院 ,合并贫血、酮症酸中毒、低血糖。例 2于 7个月起出现顽固性湿疹 ,口角、肛门周围糜烂。例 4以扭转痉挛及全身性脓疱型牛皮癣为主。例 5、6分别于 7岁、5岁起病 ,进行性肢体运动障碍 ,MRI显示颈髓炎性脱髓鞘病变。例 6伴视神经萎缩、脱发。除例 3未接受治疗外 ,5例经生物素补充治疗后疗效显著 ,皮肤损害均已控制 ,神经系统情况逐渐好转。例 4、6仍存在明显的下肢运动障碍。结论　生物素酶缺乏症患儿临床表现复杂 ,生物素补充治疗疗效显著 ,早期发现、合理治疗可有效地改善预后。对可疑患者应及早进行尿有机酸分析和血清生物素酶测定等有关?Objective To investigate the clinical and neurodevelopmental profiles of patients with biotinidase deficiency and to determine the efficacy of current therapy with respect to outcome.Methods Six patients aged from 3 months to 14 years with biotinidase deficiency were confirmed by urinary organic acid analysis with gas chromatography/mass spectrometry (GC/MS) and biotinidase assay on dried blood spots. Biotin was supplemented individually (10 ～40 mg/d). Their clinical features, laboratory findings, and treatment regimen were reviewed.Results All the 6 patients presented with some extent of neurological abnormalities and dermatological lesions. Cases 1 3 had poor feeding, vomiting, seizures, mental retardation, and lethargy onset from their early infancy, with varied degree of anemia, ketosis, acidosis, and hypoglycemia. Case 2 exhibited eczema and dermatitis from his age of 7 months. Case 4 displayed motor deficit and ataxia after 6 months of age, and generalized pustular psoriasis when he was 8 months old. Cases 5 and 6 gradually showed muscle weakness and paraplegia at the age of 7 years and 5 years, respectively. Inflammatory demyelination changes of cervical cord were evident on magnetic resonance imaging in these two patients. Case 6 had progressive optic atrophy, eczema and alopecia. Remarkable elevations of urinary lactate, pyruvate, 3 OH propionate, methylcitrate, propionylglycine, 3 OH isovalerate, 3 methylcrontonylglycine were confirmed in cases 1, 2, 3 and 5. Slight increase of urinary lactate, pyruvate, and 3 methylcrontonylglycine was observed in cases 4 and 6. Biotinidase activities assayed on dried blood spots from all the patients were below 0.1 pmol/(min·3 mm) Biotin supplementation for all the patients, except for case 3 who was not treated, resulted in pronounced and rapid clinical and biochemical improvement. Cases 4 and 6 had residual neurological damage comprising ataxia and motor handicap of legs, due to prolonged disease course.Conclusions Biotinidase deficiency intensively

关 键 词：生物素酶缺乏症 诊断 治疗 酰胺基水解酶类 生物素 碎片质谱法 

分 类 号：R725.8[医药卫生—儿科]