Supplementary Material for: Lysinuric Protein Intolerance: not only a disorder for pediatric nephrologists. Case report.

Introduction. Lysinuric Protein Intolerance (LPI) is a multisystemic inborn error of metabolism with a variable clinical expressivity, that usually begins in childhood with growth failure and gastroenterological/neurological problems related to the altered urea cycle and later complications involving the renal, pulmonary and immuno-hematological systems.
Case report: We present the case of a 40-year-old woman suffering from chronic kidney disease in the context of a LPI, whose diagnosis was challenging because the signs of the disease were always blurred and the patient never manifested critical episodes typical of this multisystemic disease. In addition to renal disease, splenomegaly, thrombocytopenia, elevated lactate dehydrogenase (LDH), hyperferritinemia and hypertriglyceridemia were also present. A thorough investigation of the patient’s food preferences revealed her spontaneous aversion to protein-containing foods and excessive drowsiness during the occurrence of infectious episodes or on the rare occasions of excessive protein intake, although without ever coming to medical attention. These nuanced signs led us to suspect an impairment of the urea cycle and ultimately allowed us to narrow down the diagnosis to LPI through biochemical and genetic investigations.
Conclusion. Nephrologists should consider LPI in the differential diagnosis, whenever a patient presents with mixed proteinuria, tubular dysfunction and/or chronic kidney failure of unknown origin. In these circumstances, we suggest looking for other signs such as growth failure, signs and symptoms ascribed to urea-cycle impairment, pulmonary involvement, hepatosplenomegaly and laboratory alterations such as pancytopenia, hyperferritinemia, lipid abnormalities, elevated LDH.

引言：赖氨酸尿性蛋白不耐受症（Lysinuric Protein Intolerance, LPI）是一种多系统先天性代谢病，临床表型多样，通常于儿童期起病，以生长发育迟缓及与尿素循环紊乱相关的消化、神经系统症状为主要表现，后续可累及肾脏、肺部及免疫血液系统。
病例报告：本文报道1例40岁女性LPI患者合并慢性肾脏病的病例。该病例的诊断颇具挑战性，因患者的疾病体征始终隐匿，从未出现该多系统疾病典型的危重发作。除慢性肾脏病外，患者还存在脾大、血小板减少、乳酸脱氢酶（LDH）升高、高铁蛋白血症及高甘油三酯血症。对患者饮食偏好的详细调研显示，其自发性厌恶含蛋白质的食物，且在感染发作期或偶发过量摄入蛋白质时会出现过度嗜睡，但此前从未因此就医。这些细微的体征促使我们怀疑存在尿素循环受损，最终通过生化与基因检测明确诊断为LPI。
结论：当患者出现不明原因的混合性蛋白尿、肾小管功能障碍和/或慢性肾衰竭时，肾内科医师应将LPI纳入鉴别诊断范畴。此类情形下，建议排查其他相关体征，如生长发育迟缓、尿素循环受损相关症状与体征、肺部受累表现、肝脾大，以及全血细胞减少、高铁蛋白血症、脂质异常、LDH升高等实验室检查异常。