Precocious familial gout with reduced fractional urate clearance and normal purine enzymes

Abstract

Gout is primarily a disease of middle-aged males and is unusual in females and adolescent males. We describe 21 young men and women (mean age 28 years) referred because of precocious onset of gout or hyperuricaemia. Fifteen patients had a family history, but known hereditary causes of primary or secondary hyperuricaemia were excluded. A high proportion (14/21) also had reduced renal function, but there was no clear relationship between this and the hyperuricaemia. Only two patients were hypertensive. A striking abnormality was that the uric acid clearance relative to creatinine [FEur] was subnormal (mean 4.4 +/- 1.4 per cent) in 15/21 patients, including all seven females. A dominantly inherited defect in renal tubular urate handling, leading to a reduced endogenous urate clearance, is the most likely explanation for the hyperuricaemia in this group. Only six patients, all male had a normal [FEur] (mean 8.6 +/- 1.0 per cent). The results confirm that young men and women with gout-or hyperuricaemia disproportionate to the renal dysfunction-should always be investigated, not only for purine defects, but also for abnormalities of renal urate handling. Since the abnormality described here was found also in symptomless subjects, the families of such patients must also be studied. Early identification is important since treatment may ameliorate the renal damage. Although rare, the number of such patients seen in a single referral unit suggests that this type of renal tubular defect in urate handling is more common than suspected and may only come to attention through an isolated episode of precocious gout, when renal function may already be impaired.