Purine disorders with hypouricemia

Hypouricemia is defined as a serum urate levels less than 2 mg/dL (119 µmol/L). Primary hypouricemia is caused by disorders of purine metabolism and transport. This laboratory finding is sometimes overlooked and, following two genetic defects, should be considered in differential diagnosis of unexplained hypouricemia. Hereditary xanthinuria is autosomal recessive and due to mutations in xanthine oxidase, leading to over-production of xanthine and minimal production of urate. Patients have very low serum urate levels and suffer from elevated levels of xanthine in the urine, leading to xanthine stones, haematuria, and sometimes occult chronic kidney failure. Hypouricemia is the key to diagnosis. Hereditary renal hypouricemia is a new genetic defect of renal transport of uric acid. Two types were distinguished: a) renal hypouricemia type 1, caused by the defects in the SLC22A12 gene coding the human urate transporter 1 (hURAT1) and b) renal hypouricemia type 2, caused by the defects in the SLC2A9 gene, which encodes GLUT9 transporter. This disorder predisposes patients to exercise-induced acute renal failure and/or nephrolithiasis. Diagnosis is based on two markers: hypouricemia (<119 µmol/L) and increased fractional excretion of uric acid (>10%). Over one hundred cases were identified in Japan and and this number is unique worldwide. Several patients were described in Macedonia. We were able to detect four Czech families with hereditary xanthinuria and eight cases of hereditary renal hypouricemia. In conclusion, hereditary xanthinuria and hereditary renal hypouricemia are still unrecognized conditions. Patients with unexplained hypouricemia need detailed purine metabolic investigations.