Originally described by Duncan and Dixon in 1960, FJHN is an autosomal dominant disease characterized by hyperuricemia, gout, and progressive renal failure. It was only recently discovered that FJHN was caused by mutations in the UMOD gene encoding the protein uromodulin, an 85 kDa glycoprotein involved in renal stone formation, the modulation of immune responses, and urothelial cytoprotection. These mutations lead to reduced renal excretion of urate. In vitro animal models of the disease suggest that the mutant forms of uromodulin cause the protein to be retained in endoplasmic reticulum, which inhibits normal trafficking to and expression at the cell surface. Patients often present in early adulthood with hyperuricemia or gout and normal blood pressure. The fractional excretion of urate is generally low. Renal dysfunction in these patients develops between ages 15-40 and is progressive, usually leading to ESRD in 10-20 years. On biopsy, patients are found to have chronic interstitial nephritis as well as thickening and splitting of the tubular basement membrane.
The optimal treatment strategy for FJHN is not clear at this time. Treatment with allopurinol to prevent gout has been recommended, though it remains uncertain as to whether or not allopurinol offers any significant benefit to preventing progression of renal disease.