Lu Zhihong, Wang Yan, Gao Langping, Lin Li, Hu Lidan, Mao Jianhua
Department of Nephrology, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children's Regional Medical Center, Hangzhou, China.
The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children's Regional Medical Center, Hangzhou, China.
Heliyon. 2023 May 6;9(5):e15993. doi: 10.1016/j.heliyon.2023.e15993. eCollection 2023 May.
Fabry disease (FD) is a rare X-linked lysosomal storage disorder. Renal involvement in FD is characterized by proteinuria and progressive renal decline. Reports on FD with nephrogenic diabetes insipidus as the initial manifestation are rare. In this paper, we report a pediatric case with an N215S variant.
A boy with an onset of polydipsia and polyuria at approximately 4 years of age was diagnosed with nephrogenic diabetes insipidus. Whole-exome sequencing showed a GLA N215S variation with no secondary cause of diabetes insipidus. No family history of polydipsia or polyuria was reported; however, the patient's maternal grandmother and her two younger brothers had hypertrophic cardiomyopathy. Both brothers required surgery due to severe cardiac involvement, and the youngest brother died of heart disease at the age of 50 years. The patient's polydipsia and polyuria worsened over the next 7 years. Serum sodium was normal, but the patient required high-dose potassium chloride to maintain normal serum potassium levels. His physical and intellectual development was normal, with no common complications of nephrogenic diabetes insipidus, such as anemia, malnutrition, vomiting, high fever, or convulsions. Dried blood spot testing showed α-galactosidase A (α-gal A) activity of 0.6 μmol/L/h and a Lyso-GL-3 level of 7.01 ng/ml. The patient developed mild proteinuria and mild myocardial hypertrophy. Renal biopsy showed myeloid bodies and zebra bodies. After more than 1 year of ERT, his urine specific gravity increased to 1.005-1.008, which was a new sign reflecting the efficacy of ERT, although urine output was maintained at 3-5 ml/kg/hour. We will continue to monitor the patient's renal tubular function and urine output.
Nephrogenic diabetes insipidus may be the initial manifestation in children with FD and/or N215S variation. In FD, the same mutation in a family may present a completely different phenotype.
法布里病（FD）是一种罕见的X连锁溶酶体贮积症。FD的肾脏受累表现为蛋白尿和进行性肾功能减退。以肾性尿崩症为初始表现的FD报道罕见。本文报告1例携带N215S变异的儿科病例。
一名约4岁起病出现烦渴和多尿的男孩被诊断为肾性尿崩症。全外显子组测序显示存在GLA N215S变异，且无尿崩症的继发原因。未报告有烦渴或多尿的家族史；然而，患者的外祖母及其两个弟弟患有肥厚型心肌病。两个弟弟均因严重心脏受累需要手术，最年轻的弟弟50岁时死于心脏病。在接下来的7年里，患者的烦渴和多尿症状加重。血清钠正常，但患者需要高剂量氯化钾来维持正常血清钾水平。他的身体和智力发育正常，无肾性尿崩症的常见并发症，如贫血、营养不良、呕吐、高热或惊厥。干血斑检测显示α-半乳糖苷酶A（α-gal A）活性为0.6 μmol/L/小时，溶酶体GL-3水平为7.01 ng/ml。患者出现轻度蛋白尿和轻度心肌肥厚。肾活检显示髓样小体和斑马小体。经过1年多的酶替代疗法（ERT），他的尿比重升至1.005 - 1.008，这是反映ERT疗效的一个新迹象，尽管尿量维持在3 - 5 ml/（kg·小时）。我们将继续监测患者的肾小管功能和尿量。
肾性尿崩症可能是FD和/或N215S变异儿童的初始表现。在FD中，一个家族中的相同突变可能呈现完全不同的表型。
