Gout as a Manifestation of Familial Juvenile Hyperuricemic Nephropathy

Abstract

We report 2 cases of familial juvenile hyperuricemic nephropathy, a rare autosomal dominant disorder characterized by uromodulin gene mutations leading to hyperuricemia secondary to profound renal uric acid underexcretion, gout, and chronic renal disease. Case 1 involves a 56-year-old woman who underwent a kidney transplant after steady decline in kidney function since the age of 19 years. Her gout had been successfully controlled with varying doses of daily allopurinol. Case 2, the son of case 1, presented with already progressive and debilitating arthritis at the age of 34 years with relatively stable chronic renal failure that was also subsequently managed with daily allopurinol and judicious anti-inflammatory prophylaxis.

A novel likely pathogenic variant in the UMOD gene in a family with autosomal dominant tubulointerstitial kidney disease: a case report

“…Mutant uromodulin inhibits trafficking and activity of NKCC2 in TAL. The resulting defect in urinary concentration and consequent mild volume depletion can secondarily increase the reabsorption of UA in the proximal tubule as a possible cause of hyperuricaemia [2,4,9].…”

“…Pathogenic variants are mainly localized to exons 3 and 4, which encode the three EGF-like domains and D8C [ 8 , 9 , 12 , 13 ]. There is no “hot spot” [ 14 ].…”