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

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 impairs nervous system and skin in the affected patients. Urinary organic acid analysis and blood biotinidase assay are crucial to the diagnosis. Early diagnosis and biotin supplementation can contribute significantly to the improvement of prognosis.