Finckh U, Kohlschütter A, Schäfer H, Sperhake K, Colombo J P, Gal A
Department of Human Genetics, University Hospital Eppendorf, University of Hamburg, Germany.
Hum Mutat. 1998;12(3):206-11. doi: 10.1002/(SICI)1098-1004(1998)12:3<206::AID-HUMU8>3.0.CO;2-E.
Carbamoyl phosphate synthetase I (CPS1) deficiency is an autosomal recessive metabolic disorder affecting the first enzymatic step of urea cycle. We report a consanguineous family in which the index patient died at 11 days of age from a severe form of CPS1 deficiency. Initial diagnosis was based on clinical histopathological, and enzymatic investigations. Direct sequencing of the complete CPS1 coding region revealed a disease-associated homozygous Thr544Met mutation in CPS1. On the basis of the molecular data, prenatal diagnosis was established for genomic DNA and performed at gestational week 12, after chorionic villus sampling. The fetus was homozygous for the Thr544Met mutation, and termination of pregnancy was elected. Histopathological signs of the hepatocellular metabolic disorder similar to that of the index patient were found in fetal liver thus giving morphological evidence for this hereditary error of urea cycle function as early as gestational week 12.
氨甲酰磷酸合成酶I（CPS1）缺乏症是一种常染色体隐性代谢紊乱疾病，影响尿素循环的第一步酶促反应。我们报告了一个近亲家庭，该家庭中的索引患者因严重的CPS1缺乏症在11日龄时死亡。初步诊断基于临床、组织病理学和酶学检查。对CPS1完整编码区进行直接测序，发现CPS1中存在与疾病相关的纯合Thr544Met突变。基于分子数据，在妊娠12周经绒毛取样后，对基因组DNA进行了产前诊断。胎儿为Thr544Met突变纯合子，遂选择终止妊娠。在胎儿肝脏中发现了与索引患者相似的肝细胞代谢紊乱的组织病理学特征，从而早在妊娠12周就为这种尿素循环功能的遗传性错误提供了形态学证据。
