Familial juvenile hyperuricemia in early childhood in a boy with a novel gene mutation

Familial juvenile hyperuricemic nephropathy (FJHN) is a rare autosomal dominant disease caused by mutations in the uromodulin (UMOD) gene. It is characterized by the development of gout, tubulointerstitial nephropathy, and end-stage renal disease. Here we report a case of FJHN that was diagnosed in early childhood in a boy with a novel gene mutation. At the age of 4 years, the patient was admitted with a diagnosis of purpura nephritis. He was discharged following symptom alleviation. However, hyperuricemia (7-9 mg/dL) and mild renal dysfunction [creatinine-estimated glomerular filtration rate (eGFR): 80-90 mL/min/1.73 m²] persisted after discharge. FJHN was suspected on the basis of a maternal family history of hyperuricemia, renal dysfunction, and dialysis. Direct sequence analysis performed at the age of 5 years revealed a novel missense mutation (c766T > G), p.Cys256Gly, in exon 3. Urate-lowering therapy was started, which provided good uric acid control (6.0 mg/dL). At the age of 8 years, persistent renal dysfunction was observed (eGFR: 80-90 mL/min/1.73 m²). Interestingly, cases of FJHN with c744C > G (p.Cys248Trp) mutations also exhibit a high incidence of juvenile onset, and identical disulfide bridges are considered responsible for the accumulation of mutant UMOD in the endoplasmic reticulum. Pediatricians should consider UMOD mutation analysis for families with autosomal dominant tubulointerstitial kidney disease (ADTKD) and a bland urinary sediment, even if hyperuricemia is mild. Also, sex and genotype are very important prognostic factors for ADTKD caused by UMOD mutations.