First reported case of Dent Disease Type 2 in a Trisomy 21 child

Abstract

Dent disease is an X-linked recessive proximal tubulopathy predominantly affecting male children with a classic triad of low molecular weight proteinuria, hypercalciuria and nephrocalcinosis. It has marked phenotypic heterogeneity and confirmation requires genetic analysis. In Trisomy 21, renal disease is an uncommon complication and frequently includes congenital abnormalities of the kidney and urinary tract (CAKUT) and renal malformations, but Dent disease has never been reported in these patients to date. We present a 6-year-old boy with Trisomy 21 who developed non-nephrotic range low molecular weight proteinuria without hypoalbuminemia or oedema. Whole exome sequencing identified a pathogenic variant in the OCRL gene (c.314T > A) and confirmed the diagnosis of Dent Disease Type 2. This is the first reported case of Dent Disease Type 2 in a Trisomy 21 child. Hypotonia and cognitive impairment can overlap in both conditions but the renal manifestations unmasked the clinical diagnosis of Dent disease type 2