Familial juvenile hyperuricemic nephropathy: Report on a new mutation and a pregnancy

BACKGROUND: Familial juvenile hyperuricemic nephropathy (FJHN) is a rare autosomal dominant disease caused by mutations in the uromodulin gene (UMOD) and leading to gout, tubulointerstitial nephropathy and end-stage renal disease.

CASE REPORTS AND RESULTS: A Latvian family suffering from FJHN is described. The father of the family developed ESRD at age 36. His daughter was diagnosed with gout and chronic kidney disease at age 14 years. A renal biopsy revealed tubulointerstitial disease; 2 sons were diagnosed at age 9 and 4 with elevated uric acid levels and reduced fractional uric acid excretion. Urinary uromodulin was normal in the younger boy, but markedly decreased in the 2 other patients. Genetic analysis revealed a previously undescribed D196Y mutation in the UMOD gene. The female patient became pregnant at age 23. During pregnancy serum creatinine decreased from 2.0 to 1.5 mg/dl and blood pressure remained low. Analysis of the baby's umbilical cord blood and a mouth swab showed the presence of the D196Y mutation. Its urinary uromodulin excretion was in the low normal range.

CONCLUSION: The uromodulin excretion pattern observed in the investigated family suggests that urinary uromodulin decreases in FJHN from low normal values at childhood to extremely low levels in early adulthood. In addition, this first report on pregnancy in a patient with FJHN shows normal adaptation despite markedly reduced renal function.