甲基丙二酸血症14例诊断及治疗分析

目的 探讨甲基丙二酸血症(MMA)的临床特征和治疗方法。方法 对14例MMA患儿的临床资料进行总结分析。结果 14例中男4例,女10例,发病年龄自出生～9岁,生后1个月内发病者7例(50％),1岁以内发病者共10例(71％)。主要临床表现有嗜睡(6例)、智力体力发育落后或倒退(7例)、惊厥(6例)、发作性呕吐(4例)、喂养困难(4例)、肌张力异常(低下5例,增高3例)、毛发黄(4例)等。血气分析提示代谢性酸中毒6例,高氨血症5例,酮尿4例,气相色谱-质谱法(GC/MS)尿有机酸分析显示14例患儿尿甲基丙二酸浓度均明显高于正常,头颅CT检查6例中5例异常,MRI检查5例全部异常,4例肌电图中2例提示有周围神经病变。3例在确诊前死亡,11例确诊患儿中10例接受维生素B12(VitB12)治疗,辅以低蛋白饮食及左旋肉碱治疗。对治疗的7例进行3个月～1年6个月(平均8.5个月)的随访,1例临床症状完全消失,4例明显好转,2例死于严重代谢性酸中毒。结论 嗜睡、智力体力发育落后或倒退、惊厥、发作性呕吐、喂养困难、肌张力异常、毛发黄、代谢性酸中毒、高氨血症、酮尿是MMA的主要临床特征,GC/MS法尿有机酸分析是早期诊断MMA的重要依据,确诊后坚持长期合理治疗是改善预后的有效方法。

Diagnosis and treatment of methylmalonic acidemia in 14 cases

Objective Methylmalonic acidemia (MMA) is one of the most common disorders of congenital organic acid metabolism. This study aimed at exploring the clinical characteristics and treatment of the disease to help improve our understanding of it. Methods The clinical data of 14 patients with MMA admitted to our hospital between January 2002 and July 2003 were analyzed and the diagnoses were confirmed by gas chromatography/mass spectrometry (GC/MS). The patients consisted of 4 males and 10 females, whose age of onset ranged from birth to 9 years with 7 cases younger than 1 month (50% ) and 10 cases younger than 1 year (71%). Results The main clinical manifestations were lethargy (6 cases), developmental retardation or regradation (7 cases) , convulsion (6 cases) , recurrent vomiting (4 cases) , difficulty with feeding (4 cases) , muscular dystonia (5 cases with hypotonia, 3 with hypertonia) and yellowish hair (4 cases) , etc. Some cases were also presented with hair loss, hepatomegaly, ataxic or stiff gait, and motor weakness with muscular atrophy. The laboratory findings showed metabolic acidosis in 6 cases, hyperammonemia in 5 cases, ketonuria in 4 cases and remarkable elevation of urinary methylmalonic acid concentration in all cases. Some abnormalities in globus pallidus and cerebral white matter as well as diffuse cerebral atrophy were noted by the brain CT and MRI in 5 respective cases, while 4 cases did not receive neuroradiological examinations. Peripheral neuropathies were found by electromyography in 2 patients and bilateral optic nerve atrophy was detected by eyeground examination in 1 child. Three patients died before the diagnoses were made. Of the 11 survivals, 10 children have received therapy of vitamin B12 (VitB12) and supplementation of L-carnitine with restricted-protein diet The follow-up for a period ranging from 3 months to 1. 5year ( mean 8. 5 months) of 7 cases with medical therapy showed a favorable outcome without any symptoms in 1 case and apparent improvement in 4 cases (the diffuse cerebral atrophy in MRI completely recovered in one case) , however, 2 patients died from severe metabolic acidosis. Conclusions The main clinical features of MMA include lethargy, developmental retardation or regradation, convulsion, recurrent vomiting, difficulty with feeding, muscular dystonia, yellowish hair, metabolic acidosis, hyperammonemia and ketonuria, etc. Urine organic acids analysis with GC/MS is critical to the early diagnosis of MMA. Early diagnosis and appropriate long-term treatment are essential to improve the prognosis of the disease.