van de Logt Anne-Els, Kluijtmans Leo A J, Huigen Marleen C D G, Janssen Mirian C H
Department of Internal Medicine, Radboud University Medical Center, 9101, 6500 HB, Nijmegen, The Netherlands.
Department of Laboratory Medicine, Translational Metabolic Laboratory (TML), Radboud University Medical Center, Nijmegen, The Netherlands.
JIMD Rep. 2017;31:95-99. doi: 10.1007/8904_2016_565. Epub 2016 May 5.
A 59-year-old woman, with a medical history of intellectual disability after perinatal asphyxia, was admitted because of coma due to hyperammonemia after she was treated for a fracture of the pelvis. The ammonia level was 280 μM. Acquired disorders as explanation for the hyperammonemia were excluded. Metabolic investigations showed an elevated glutamine and alanine and low citrulline, suspect for a urea cycle defect (UCD). Orotic acid could not be demonstrated in urine. DNA investigations were negative for mutations or deletions in the OTC and CPS1 gene, but revealed a homozygous c.603G>C mutation in exon 2 of the N-acetylglutamate synthase (NAGS) gene (NM_153006.2:c.603G>C), which mandates p.Lys201Asn. This is a novel mutation in the NAGS gene.After the diagnosis of NAGS deficiency was made carbamylglutamate was started in a low dose. In combination with mild protein restriction the ammonia level decreased to 26 μM.This is one of the first patients in literature in whom the diagnosis of a UCD is made at such an advanced age. It is important for the adult physician to consider a metabolic disorder at every age.
一名59岁女性，有围产期窒息后智力残疾的病史，因骨盆骨折治疗后出现高氨血症昏迷入院。氨水平为280μM。排除了作为高氨血症解释的后天性疾病。代谢检查显示谷氨酰胺和丙氨酸升高，瓜氨酸降低，怀疑存在尿素循环缺陷（UCD）。尿中未检测到乳清酸。DNA检查显示OTC和CPS1基因无突变或缺失，但在N - 乙酰谷氨酸合酶（NAGS）基因（NM_153006.2:c.603G>C）外显子2中发现纯合的c.603G>C突变，该突变导致p.Lys201Asn。这是NAGS基因中的一个新突变。在诊断为NAGS缺乏症后，开始低剂量使用氨甲酰谷氨酸。结合轻度蛋白质限制，氨水平降至26μM。这是文献中首批在如此高龄时被诊断出患有UCD的患者之一。对于成年医生来说，在每个年龄段都考虑代谢紊乱很重要。
