鸟氨酸氨甲酰基转移酶缺陷症1例临床及OTC基因突变分析

Clinical and OTC gene mutation analysis of one child with ornithine transcarbamylase deficiency

目的 分析1例鸟氨酸氨甲酰基转移酶缺陷症（OTCD）的临床和基因突变特点,以提高对该疾病的认识.方法 分析OTCD患儿1例（女,14个月）.收集该患儿临床资料,抽取患儿及其父母的静脉血2 mL,应用聚合酶链反应扩增OTC基因的各个外显子及相邻内含子所在的片段,并进行直接测序,以检测突变.结果 本例迟发型OTCD患儿,病程3个月,间断嗜睡、呕吐,且伴有肢体震颤、精神运动发育倒退,此次以小脑共济失调为主要表现就诊.头部磁共振示病变严重.血生化示轻度肝损伤,血氨增高,尿气相色谱-质谱分析提示尿嘧啶和乳清酸增高.OTC基因检测示患儿母亲及患儿位于第8外显子c.852C＞G（p.Y284X）,为错义突变,母亲表型正常.结论 OTCD临床表现为高氨血症及其所引起的不同程度的神经系统和肝损伤等,临床表现缺乏特异性,易误诊.血氨、尿代谢病筛查、血氨基酸分析、基因检查有助于早期明确诊断.治疗上早干预,长期管理血氨水平,避免高氨血症发生,可改善预后.

Objective To analyze the clinical and OTC gene mutation characteristics of 1 case with ornithine transcarbamylase deficiency （OTCD） and to deepen the understanding of OTCD.Methods One case of 14-month female OTCD patient was analyzed.Clinical data of the child patient was collected and venous blood 2 mL from the patient and her parents was extracted respectively.Polymerase chain reaction was used to amplify the fragment where various exon of OTC and its neighboring intron were distributed, followed by direct sequencing to detect mutation.Results It was showed that late-onset OTCD child patient had contracted the disease for 3 months,with intermittent drowsiness, vomiting and psychomotor development regression.Cerebellar ataxia was the main symptom of the child patient when she was taken to Tianjin Children＆#39;s Hospital.According to brain MRI, the lesion was severe.Blood chemistry showed mild hepatic lesion and increased blood ammonia.According to urine gas chromatography mass spectrometry analysis,there was a rise in uracil and orotic acid.OTC genetic testing showed the child patient and her mother were in the 8th exon,c.852C 〉 G （p.Y284X）.Missense mutation occurred in this locus.The mother had normal phenotype.Conclusions Clinically OTCD has the symptoms of hyperammonemia and the resulting in varying degrees of damage to the nervous system and the liver.Without clinical specificity, this disease is easy to be misdiagnosed.Methods like blood ammonia and urine metabolic disease screening, blood amino acid analysis and genetic testing help confirm the disease earlier.As for treatment, early intervention and chronic control of blood ammonia level to guard against hyperammonemia will lead to better curative effect.