Urine Spot Beta2-Microglobulin as a Screening Tool for Dent Disease Type 1

Abstract

Dent disease type 1 (DD1) is a rare X-linked proximal tubulopathy caused by pathogenic variants in CLCN5 gene. It typically presents in childhood with low-molecular-weight proteinuria, hypercalciuria, and variable progression to chronic kidney disease. Early diagnosis is often missed because routine urine dipstick testing detects only albumin and underestimates tubular protein losses. We describe two boys who presented with isolated proteinuria, in whom a marked discrepancy between minimal dipstick albuminuria and elevated 24-h urinary protein excretion raised suspicion for tubular proteinuria. Urine β2-microglobulin levels were markedly increased in both children, supporting proximal tubular dysfunction. Hypercalciuria was identified despite normal serum studies and normal renal ultrasonography. Genetic testing confirmed CLCN5 variants consistent with DD1. The first patient had a de novo large deletion involving exons 3–15, and maternal testing confirmed the absence of carrier status. The second patient carried a familial 3-bp insertion in exon 10 that was reclassified as pathogenic following segregation analysis, with his mother being identified as a heterozygous carrier. Both children were started on angiotensin converting enzyme inhibitors for management of proteinuria. These cases highlight the importance of recognizing tubular proteinuria in children with unexplained proteinuria. Measurement of urine β2-microglobulin is a simple, inexpensive, and highly sensitive tool that can prompt timely evaluation for DD1. Early integration of biochemical markers with targeted genetic testing is essential for accurate diagnosis and appropriate management of this rare but clinically significant condition.