新生儿鸟氨酸氨甲酰基转移酶缺乏症一例及孕母围产期管理

Muitidisciplinary perinatal management of a woman and her baby with ornithine transcarbamylase deficiency

目的提高对新生儿鸟氨酸氨甲酰基转移酶缺乏症（ornithine carbamoyltransferase deficiency，OTCD）的临床和基因特征的认识，并探讨新生儿期发病的OTCD患儿治疗及迟发型OTCD孕妇的围产期综合管理。方法总结2013年4月上海交通大学医学院附属新华医院收治的1例OTCD患儿及其母亲的临床资料，并对该家系鸟氨酸氨甲酰基转移酶（ornithine transcarbamylase，OTC）基因进行分析。结果患儿生后开始出现血氨进行性升高，生后48h血氨升高至1020μmol／L。入院第3天家属放弃治疗，患儿死亡。患儿母亲为围产期发病的OTCD患者，经药物及限制蛋白等饮食治疗，围产期及产后血氨水平基本控制在正常范围。患儿血串联质谱分析显示精氨酸升高（97．43μmol／L，参考范围：1．00～25．00μmol／L）、瓜氨酸正常（27．43μmol／L，参考范围：4．00～30．00μmol／L）、鸟氨酸升高（161．66μmol／L，参考范围：10．00～120．00μmol／L）、蛋氨酸升高（70．45μmol／L，参考范围：10．00～50．00μmol／L）；尿气相质谱分析提示尿嘧啶也升高（67．11μmol／mol肌酐）、乳清酸升高（1372．66μmol／mol肌酐，参考范围：0．00～1．50μmol／mol肌酐）。患儿母亲血串联质谱显示精氨酸正常（8．44μmol／L，参考范围：1．50～25．00μmol／L）、瓜氨酸正常（8．41μmol／L，参考范围：7．00～35．00μmol／L）、谷氨酸升高（279．15μmol／L，参考范围：45．00～200．00μmol／L）；尿气相质谱分析显示尿嘧啶升高（51．55μmol／mol肌酐，参考范围：0．00～7．00μmol／mol肌酐）、乳清酸升高（38．75μmol／mol肌酐，参考范围：0．00～1．50μmol／mol肌酐）。患儿OTC基因的第6外显子上存在c．583G〉A（G195R）纯合突变，患儿母亲及外祖母OTC基因的第6外显子上存在C．583G〉A（G195R）杂合突变。结论综合管理有助于使OTCD孕妇顺利渡过围产期。新生儿期起病的男性OTCD患者预后不佳。

Objective To investigate the clinical features and gene mutation of a newborn with neonatal-onset ornithine transcarbamylase deficiency （OTCD） and report the multidisciplinary perinatal management of the mother with late-onset OTCD. Methods The clinical features, biochemical data and the treatment of a newborn boy with OTCD and his mother admitted by Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine in April, 2013, were collected. The ornithine transcarbamylase （OTC） gene in the family was analyzed. Results Serum ammonium in the male newborn gradually increased to 1 020 μmol/L at 48 h after birth. His blood amino acids level and urine organic acid level showed a pattern indicative of OTCD [blood arginine （97.43 μ mol/L, reference 1.00-25.00 μmol/L）, citrulline （27.43 μ mol/L, reference 4.00-30.00 μmol/L）, ornithine （161.66 μmol/L, reference 10.00-120.00 μ mol/L） and methionine （70.45 μmol/L, reference 10.00-50.00 mol/L）; urine uracil （67.11 μ mol/mol Crea, reference 0.00-7.00 μ mol/mol Crea） and orotic acid （1 372.66 μ mol/mol Crea, reference 0.00-1.50 μmol/mol Crea）]. DNA studies revealed a c.583G 〉 A （G195R） homozygous mutation of the OTC gene. His mother was heterozygous for OTCD and developed acute hyperammonemia during pregnancy. Her blood showed a normal-leveled arginine （8.44 μ mol/L, reference 1.50-25.00 μ mol/L）, a normal-leveled citrulline（8.41 μ mol/L, reference 7.00-35.00 μ mol/L）, an elevated glutamate（279.15 μ mol/L, reference 45.00-200.00 μ mol/L）. Her urine uracil （51.55 μ mol/mol Crea, reference 0.00-7.00 μmol/mol Crea） and orotic acid （38.75 μ mol/mol Crea, reference 0.00-1.50 μ mol/mol） were elevated. Successful management of her prenatal and postpartum blood ammonia level was achieved after administration of pharmacologic nitrogen scavengers and protein limitation. DNA studies revealed a c.583G 3- A （G195R） heterozygous mutation in the newborn＇s mother and grandmother. Conclusions General management on pregnant OTCD women is effective. Male newborn oatients often have a poor prognosis.