Gout : Pathophysiology-II
Inherited enzymatic defects are amongst less common causes of gout. They include deficiency of hypoxanthine guanine phosphoribosyl transferase (HGPRT; X-linked recessive), abnormal phosphoribosylpyrophosphate synthetase (X-linked dominant), and glucose-6-phosphatase deficiency (autosomal recessive). HGPRT captures purine metabolites in the salvage pathway. Absence of HGPRT causes breakdown of purine metabolites into uric acid leading to hyperuricemia. Contributing factors to gout include: patient age (symptomatic gout usually occurs after long-standing hyperuricemia), genetic predisposition (enzyme abnormalities mentioned above, polymorphisms in URAT1 and GLUT9 genes involved in uric acid metabolism), alcoholism, obesity, diuretics (e.g. thiazides that reduce uric acid excretion), starvation, lead toxicity and chronic diseases like sarcoidosis and psoriasis. The image shows large gouty tophi around the elbow joint in a patient with chronic tophaceous gout.