【摘要】 目的探讨遗传性代谢疾病致儿童脑发育落后中治疗及影响预后的相关因素。方法用串联质谱仪对278例原因不明的脑发育落后患儿进行血氨基酸谱和酰基肉碱谱筛查,对疑似代谢性疾病患儿进行尿气相色谱/质谱(GC/MS)及相关酶活性检测,对检出的遗传性代谢病患儿的临床资料进行综合分析。结果17/278例(6.15%)确诊为遗传性代谢病,其中甲基丙二酸血症4例,甲基丙二酸血症伴同型胱氨酸尿症4例,丙酸血症3例,鸟氨酸氨甲酰转移酶缺乏症、枫糖尿病、Ⅰ型戊二酸血症、异染色性白质脑病、苯丙酮尿症、生物素酶缺乏症各1例。临床表现为智能及运动发育落后或倒退、惊厥、昏迷、呕吐、肌张力降低、营养不良、嗜睡、反复感染等。实验室检查显示代谢性酸中毒、血氨及血乳酸增高、贫血等。MRI表现为脑萎缩、双侧脑白质T2w高信号或伴T1w低信号、多发性脑软化或囊样变等。起病早、伴严重酸中毒及昏迷的维生素B12无效型甲基丙二酸血症预后极差。患儿经特殊奶方、低蛋白饮食、肉碱、维生素B12及生物素等治疗后,好转11例,死亡5例,未愈1例。结论对原因不明的脑发育落后患儿应予遗传代谢性病筛查;早期、合理治疗有助于改善预后。更多还原

【Abstract】 Objectives To investigate the treatment and prognostic factors of developmental delay in children caused by inborn errors of metabolism. Methods Two hundred and seventy-eight patients with developmental delay were enrolled in the study. Blood amino acids and acylcarnintines profiles were tested with tandem mass spectrometry. Gas chro- matography / mass spectrometry (GC / MS) analysis of urine and enzyme activity tests were further made when the patients were suspected to have metabolic disorders. Clinical data of the patients with inborn errors of metabolism were also ana- lyzed. Results Seventeen of 278 patients (6.15% ) with metabolic disorders were confirmed, including methylmalonic acidemia (MMA)(4), methylmalonic acidemia complicated with homocystinuria (4), propionic acidemia (PA) (3), ornithine transcarbamylase deficiency (1), maple syrup urine disease (1), glutaric acidemia typeⅠ (1), metachromatic leukodystrophy (MLD)(1), phenylketonuria (1), and biotinidase deficiency (1) . The clinical manifestations were di- verse, including mental retardation or regression, seizure, coma, vomiting, hypotonia, malnutrition, lethargy, frequent infections, etc. Laboratory findings included metabolic acidosis, hyperammonemia, hyperlacticemia, and anemia. MRI findings included cerebral atrophy, a pattern of T2 higher signal intensity and / or T1 lower signal intensity in cerebral white matter and multiple encephalomalacia or cystic changes, etc. MMA patients, early-onset with severe acidosis and coma, with no response to the treatment of vitamin B12, had a poor prognosis. Improvement was observed in 11 patients after treatment with special milk, low-protein diet, carnitine, vitamin B12 and biotin, etc. Four MMA patients and 1 PA pa- tients died, 1 MLD patient unchanged. Conclusions Screening tests of inherited metabolic disorders should be performed in children with developmental delay with unknown etiology. Early diagnosis and appropriate treatment might improve the prognosis.更多还原