迟发型鸟氨酸氨甲酰基转移酶缺乏症8例临床表现及OTC基因分析

Clinical features of late-onset ornithine transcarbamylase deficiency and their OTC gene mutations:An analysis of 8 cases

目的总结急性发病的迟发型鸟氨酸氨甲酰基转移酶缺乏症(ornithine transcarbamylase deficiency,OTCD)的临床及基因突变特点,提高快速识别与诊治的能力。方法对2014年1月至2017年12月在郑州大学附属儿童医院确诊为OTCD的8例患儿临床表现、实验室检查、血氨基酸、尿有机酸及基因突变进行回顾性分析,总结OTCD的诊疗要点。结果 8例患儿中男性3例,女性5例,于10个月至6岁10月龄时初诊,5例发病前健康,3例既往智力运动发育落后;主要临床表现为呕吐、食欲下降、意识障碍、惊厥等;检查发现肝损伤,血氨显著增高,血瓜氨酸降低,尿乳清酸、尿嘧啶增高,鸟氨酸氨甲酰基转移酶(OTC)基因各检出不同的致病突变,其中c.118C>T、c.482A>G、c.898del T、c.275G>A、c.803T>C为5种已知突变,c.67C>T、c.416T>G、c.898dup T为3种新突变。经血液净化等治疗后,4例患儿好转,4例放弃治疗后死亡。结论 OTCD是一种严重的尿素循环障碍疾病,临床表现缺乏特异性,个体差异显著。血氨检测是发现OTCD的关键,对不明原因的呕吐、意识障碍患儿应高度重视,代谢分析及基因分析是确诊的关键,及早诊疗可改善预后。

Objective To improve the ability of rapid identification and diagnosis of late-onset ornithine transcarbamylase（OTC）deficiency by summarizing the clinical and mutations features of eight cases. Methods The clinical manifestation,laboratory examination,blood amino acids,urinary organic acids and gene analysis of 8 patients with OTC deficiency treated in Children＇s Hospital Affiliated to Zhengzhou University from Jan.2014 to Dec.2017 were studied. The points of diagnosis and treatment for OTC deficiency were summarized. Results Eight children（3 boys and 5 girls）first visited the emergency department of our hospital at the age from 10 months to 6 years and 10 months due to vomiting,loss of appetite,conscious disturbance and convulsions. Liver dysfunction,significantly elevated blood ammonia,decreased blood citrulline,and elevated urine orotic acid and uracil were found by laboratory tests. Different mutations in their OTC gene were identified from these patients. Five mutations,c.118 CT,c.482 AG,c.898 del T,c.275 GA and c.803 TC,were reported. c.67 CT,c.416 TG and c.898 dup T were novel mutations. After hemofiltration and other active symptomatic treatment,4 patients were improved,while the other 4 patients who discontinued treatment died soon. Conclusion OTC deficiency is a severe urea cycle disorder with significant individual differences. The patients are usually lack of specific clinical manifestations. For the patients with vomiting of unknown reasons and disturbance of consciousness,blood ammonia test is the key to the diagnosis. Metabolic studies and genetic studies are important to confirm the diagnosis. Early treatment can improve the prognosis.