Al-Qattan Sarah, Malcolmson Caroline, Mercimek-Andrews Saadet
Division of Clinical and Metabolic Genetics, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Ontario, Canada.
Division of Hematology, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Ontario, Canada.
Mol Genet Metab Rep. 2021 Mar 13;27:100741. doi: 10.1016/j.ymgmr.2021.100741. eCollection 2021 Jun.
We report a 9-year-old boy with lysinuric protein intolerance (LPI). He had developmental delay, short stature, failure to thrive, high-protein food aversion, hypothyroidism, growth hormone deficiency, features of hemophagocytic lymphohistiocytosis (HLH), decreased bone mineral density and multiple thoracic spine compression fractures on X-ray. LPI was suspected, but urine amino acid profile and normal orotic acid did not suggest biochemical diagnosis of LPI. Targeted next generation sequencing panel for HLH (including ) was organized. Due to elevated glutamine in plasma amino acid analysis, a metabolic consultation was initiated and his asymptomatic post-prandial ammonia was 295 μmol/L. We then suspected -acetylglutamate synthase or carbamoyl-phosphate synthase I deficiency due to marked hyperammonemia, elevated glutamine level, normal orotic acid, and normalization of ammonia at 2 h of carglumic acid (200 mg/kg/d). His targeted next generation sequencing panel for HLH revealed homozygous pathogenic variant in ((NM_001126106.2): c.726G>A (p.Trp242*)) and confirmed the diagnosis of LPI. We emphasize the importance of genetic investigations in the diagnosis of LPI.
我们报告了一名9岁的赖氨酸尿性蛋白不耐受（LPI）男孩。他有发育迟缓、身材矮小、生长发育不良、对高蛋白食物厌恶、甲状腺功能减退、生长激素缺乏、噬血细胞性淋巴组织细胞增生症（HLH）的特征、骨密度降低以及X线显示多个胸椎压缩性骨折。怀疑为LPI，但尿氨基酸谱及正常乳清酸不支持LPI的生化诊断。于是组织了针对HLH的靶向二代测序 panel（包括……）。由于血浆氨基酸分析中谷氨酰胺升高，启动了代谢会诊，其无症状餐后血氨为295 μmol/L。鉴于显著高氨血症、谷氨酰胺水平升高、乳清酸正常以及服用卡谷氨酸（200 mg/kg/d）2小时后血氨正常，我们随后怀疑是N - 乙酰谷氨酸合酶或氨甲酰磷酸合酶I缺乏。他针对HLH的靶向二代测序panel显示SLC7A7（NM_001126106.2）存在纯合致病性变异：c.726G>A（p.Trp242*），从而确诊为LPI。我们强调基因检测在LPI诊断中的重要性。
