【作者】 李东；

【导师】 宋力；

【作者基本信息】 天津医科大学 ， 儿科学， 2011， 硕士

【摘要】 目的：有机酸尿症(organic aciduria)又称有机酸血症(organic acidemia),是儿童遗传代谢性疾病中较常见的病种,目前已发现50余种。有机酸尿症临床表现复杂多样,多导致严重神经系统损害,给家庭和社会带来沉重的负担。气相色谱/质谱联用(gas chromatography/mass spectrometry, GC/MS)尿有机酸分析是确诊有机酸尿症的有效方法。早期诊断、早期治疗可有效改善预后。但由于条件限制,目前此类疾病不能进行全面筛查,所以熟悉有机酸尿症临床和实验室特征是及时进行GC/MS尿有机酸分析、早期诊断及合理治疗的前提及关键,从而为降低患儿致残率、改善生活质量奠定基础。方法：对26例甲基丙二酸尿症(methylmalonic acaduria, MMA)、5例戊二酸尿症Ⅰ型(glutaric acaduria type I,GA1)、4例丙酸血症(propionic academia,PA)共35例有机酸尿症患儿就发病年龄、起病方式、临床表现、家族史、既往史、诊断和鉴别诊断、治疗及预后等临床特征进行分析；同时分析患儿血液生化、气相色谱/质谱联用尿有机酸、影像学、脑电图及脑干电测听等实验室检查。结果：1 35例患儿中22例1岁前发病,平均发病年龄8个月。2 28例患儿急性起病,其中24例发病前有感染或高蛋白饮食。3主要临床表现：精神运动发育或智力落后26例,其中精神运动发育倒退5例。有间断呕吐病史18例,喂养困难16例,伴有抽搐12例,呼吸急促9例,发作性嗜睡8例,面色苍白8例,肌张力减低8例,肌张力增高7例,营养不良6例,意识障碍6例,共济失调5例,锥体外系症状5例,大头畸形5例(均为戊二酸尿症Ⅰ型),消化道出血3例,瘫痪2例。4 18例患儿既往被当地医院诊断为“胃肠炎、胰腺炎、脱水”,“脑积水”,“脑炎”,“脑瘫”,“蛛网膜囊肿”。5 12例患儿有母亲不明原因流产、死胎史,同胞死亡史,精神运动发育落后或智力低下等异常家族史。6实验室检查：全部患儿气相色谱/质谱联用(GC/MS)尿有机酸分析异常。35例患儿中,代谢性酸中毒25例,贫血12例,乳酸增高11例,肝功能异常10例,高氨血症6例,肾功能异常6例,粒细胞减少5例,血小板减少4例。头颅MRI检查30例,均异常,表现为脑外间隙增宽28例,脑室增宽24例,髓鞘发育延迟16例,基底节异常信号12例,硬膜下积液6例,颅内出血3例。脑电图检查35例,异常25例,表现为背景慢活动增多、癫痫样放电。脑干电测听检查15例,异常9例,表现为外周或脑干段异常,听阈升高。7治疗及预后：急性期主要是改善内环境、保证热量、控制感染、惊厥。30例患儿接受长期治疗,包括低蛋白饮食、左旋肉碱、维生素B2、维生素B12治疗,随访1月～5年,18例精神运动发育明显好转,3例仍有抽搐发作,1例死亡。5例失访。结论：有机酸尿症临床表现复杂多样,多数1岁内急性起病,诱因多为感染、高蛋白饮食,其临床表现及实验室特征为精神运动发育落后或倒退、呕吐、喂养困难、肌张力异常、惊厥、锥体外系症状、代谢性酸中毒、高氨血症、肝功能异常、贫血等,多导致严重神经系统损害。头影像学、普通血生化检查可提供有价值的诊断线索,对于原因不明的智力运动障碍、惊厥、代谢异常等患儿应及早进行GC/MS尿有机酸检查。早期诊断、早期治疗是改善预后的关键。更多还原

【Abstract】 ObjectiveOrganic aciduria, also called organic acidemia, is the most frequent inherited metabolic disease among children. So far, more than 50 types of organic acidemias have been found. With complicated and diverse clinical manifestations, most of organic acidemias impair the nervous system seriously and bring heavy burden to the family and society. GC/MS is a very useful method for the screening and diagnosis for organic acidemias. Early diagnosis and adequate treatment contribute a lot to improve the neurological prognosis of the patients. However, due to constraints, we can not present a comprehensive screening of organic acidurias, so getting familiar with the clinical and laboratory characteristics of organic acidurias is premise and key to the timely GC/MS, early diagnosis and proper treatment, so as to lay the foundation of reducing the disability rate of children and also improving life quality.MethodsA total of 35 cases of organic aciduria children (including 26 cases of methyl-malonic aciduria,5 cases of glutaric aciduria type I and 4 cases of propionic acidemia) were analyzed with a series of clinical characteristics including onset age, type of onset, clinical manifestations, family history, past history, diagnosis and differential diagnosis, treatment and prognosis; Also biochemistry examination, urinary organic acids detected by gas chromatography/mass spectrometry(GC/MS), imaging, EEG and BAEP were analyzed.Results1.22 cases of children precipitated before first year of life, and the average onset age is 8 months.2.28 patients had gone through acute onset,24 cases of which had infection or high-protein diet before onset.3. The main clinical manifestations are:psychomotor development or mental retardation (n=26), psychomotor development back(n=5), a history of intermittent vomiting(n=18), feeding difficulties (n=16), seizures (n=12), shortness of breath (n=9), attacks of drowsiness (n=8), pale (n=8), muscle tension reducing(n=8), muscular hypertonia (n=7), malnutrition(n=6), disturbance of consciousness(n=6), ataxia(n=5), extrapyramidal symptoms(n=5), abnormal bigness of the head in 5 cases (all of them are glutaric aciduria type I), gastrointestinal bleeding (n=3) and paralysis(n=2).4.18 cases of children were once diagnosed as"gastroenteritis, pancreatitis, dehydration, hydrocephalus, encephalitis, cerebral palsy or arachnoid cyst" by local hospitals.5. Mothers of 12 patients had unexplained miscarriage, stillbirth history, siblings death history psychomotor retardation, or family history of mental retardation and other abnormalities.6. Laboratory examination:the urinary organic acids of all patients analyzed by gas chromatography/mass spectrometry were presented abnormalities. Abnormal biochemistry examination including:metabolic acidosis (n=25), anemia(n=12), lactic acid increased (n=11), liver dysfunction (n=10). hyperammonemia (n=6), renal dysfunction (n=6), neutropenia (n=5), thrombocytopenia(n=4). Abnormal cranial MRI examination of 30 cases including:brain extracellular space widened (n=28), ventricles widened (n=24), delayed myelination (n=16), abnormal signal in basal ganglia (n=12), subdural effusion (n=6), intracranial bleeding (n=3). The EEG showed that a 25 of total presented slow activity.spike and slowly discharge. The BAEP showed that 9 cases in 20 presented abnormalities in section of the peripheral or brain stem, and increased hearing threshold.7. Treatment and prognosis:during the acute phase, improving the internal environment, guaranteeing the heat, controlling infection and convulsions are essential.30 cases of children, followed up for 1 month to 5 years, accepted long-term treatment including the low-protein diet, carnitine, vitamin B2, vitamin B12 treatment,18 cases showed significant improvement in psychomotor development; 3 cases are still with convulsion; 1 patient died and 5 cases withdrew. ConclusionWith complicated and diverse clinical manifestations, most patients of organic acidemias have acute onset with inducements of infection and high-protein diet. The clinical and laboratory features of organic acidemias are psychomotor retardation or regression, vomiting, feeding difficulties, abnormal muscle tone, convulsions, extrapyramidal symptoms, metabolic acidosis, hyperammonemia, abnormal liver function, anemia etc. Organic acidemia can cause serious neurological damage. Cephalometry and blood biochemical tests can provide valuable diagnostic clues,, those who had unknown-reasoned intellectual and movement disorders, seizures and metabolic abnormalities shall be carried GC/MS examination of urine organic acids early. Early diagnosis and adequate treatment contribute a lot to improve the neurological prognosis of the patients.更多还原