Abstract
Dent disease 1 is a rare X-linked recessive inherited disease, caused by pathogenic variants in the chloride voltage-gated channel 5 (CLCN5) gene. Dent disease 1 is characterized by low molecular weight (LMW) proteinuria, hypercalciuria, nephrocalcinosis, and chronic kidney disease. Infants may manifest only asymptomatic LMW proteinuria, which increases the difficulty of early diagnosis. We describe two male infants presenting only with nephrotic-range LMW proteinuria observed on examination using urine protein electrophoresis. Hereditary renal tubular diseases were highly suspected based on early onset age and LMW proteinuria. Thus, next-generation sequencing (NGS) was performed and pathogenic mutations in CLCN5 were identified in both patients. A diagnosis of Dent disease 1 was established based on the above informations. The two patients developed hypercalciuria during late follow-up, which verified the diagnosis. These two cases highlight the importance of next-generation sequencing in the early diagnosis of Dent disease 1 with only LMW proteinuria.
Highlights
Dent disease 1 (OMIM 300009) is a proximal renal tubular dysfunction that occurs mostly in males
We describe two male infants who presented with only the symptom of nephrotic-range low molecular weight (LMW) proteinuria and in whom next-generation sequencing (NGS) was used in the early diagnosis of Dent disease 1
Urine protein electrophoresis is an effective way for finding LMW proteinuria [17], which shows as excessive urinary loss of α1-microglobulin, β2-microglobulin, or other LMW plasma proteins
Summary
Dent disease 1 (OMIM 300009) is a proximal renal tubular dysfunction that occurs mostly in males. We describe two male infants who presented with only the symptom of nephrotic-range LMW proteinuria and in whom NGS was used in the early diagnosis of Dent disease 1. The same mutation site was reported in another Dent disease 1 case [12], who showed hematuria, proteinuria, hypercalciuria, renal phosphate wasting, aminoaciduria, β2-microglobulinuria, and active Rickets at 2 years old. A815G,p.Y272C) in the exon of the CLCN5 gene (ChrX:49850995) His mother with heterozygous mutations (Figure 2, Patient 2) has not shown any related symptoms. This mutation is found to be another pathogenic variant of Dent disease 1 in accordance with the ACMG Mutation Criteria Guideline
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