Lysinuric protein intolerance mimicking N-acetylglutamate synthase deficiency in a nine-year-old boy

Abstract 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 SLC7A7) 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 n-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 SLC7A7 ((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.