Gout is a systemic disease characterized by joint inflammation typically caused by high serum uric acid levels and precipitation of monosodium urate crystals. Common symptoms of gout include rapid development of arthritis with increased redness and painful inflammation at joints accompanied by severe painful attacks often at night. Deficiencies in renal urate transportation have been linked to genetic mutations that give rise to abundance in uric acid production and/ or scarcity in its excretion. A recent survey showed that the worldwide incidence of gout increases every year due to unhealthy lifestyle and dietary choices. Foods like red meat, organ meat, shellfish, beer, high-fructose corn syrup are linked to an increased risk of gout. Higher prevalence of gout in men and postmenopausal women has been explained by the deficiency in female hormones which increases uric acid excretion from the body.
Molecular pathogenesis
Gout is closely linked with hyperuricemia, which is also characterized by high levels of uric acid in the serum. When uric acid levels go over threshold, it results in the accumulation and formation of uric acid crystals. However, many hyperuricemic patients remain asymptotic and do not get gout. Upon ionization uric acid is converted to urate. Excess urate crystals accumulate in joints and cause painful inflammation. Generally, serum uric acid levels are maintained in the body by balancing production and excretion levels. Uric acid may be produced in-house via cell-turnover or from foods containing purine. Ultimately it is excreted through the kidneys and gastrointestinal tract. Enzymes involved in metabolism of purines are deficient or inactive in gout patients. This deficiency leads to the abundance in uric acid production. Specifically, two such enzymatic abnormalities have been found to clinically manifest as gout. The Lesch-Nyhan syndrome is an X-linked recessive disorder that, in addition to development of renal stones, involves neurological abnormalities such as dystonia, cognitive dysfunction, and self-mutilation because of a deficiency in hypoxanthine–guanine phosphoribosyl transferase enzyme. The other disorder known to cause gout in younger patients stems from increased activity of phosphoribosyl pyrophosphate synthetase, that ultimately leads to arthritis and uric acid renal stones. Additionally, SLC22A12, SLC2A9 and SLC17A3 are some among the many genes critical in regulation of uric acid levels and encode for transporter proteins present on renal tubules. Mutations in these genes has been linked to the clinical manifestation of gout disease.
Dietary influence
Foods containing metabolites that cause gout generally include animal- or seafood-based cooked or processed items linked to increased serum uric acid levels. Alcohol over-consumption is among the top risk-factors for increased incidence of gout. Specifically, consumption of beer showed the maximum correlation to increased levels of uric acid. However, foods that are rich in purines such as beans, lentils legumes, dairy products, and mushrooms are not associated with increased risk of gout incidence. Interestingly, diets rich in Vitamin C were found to cause increase renal excretion of uric acid, making it a possible prescribed supplement for patients dealing with gout or hyperuricemia. Treatment options for gout currently include subsiding acute painful inflammatory flares using oral or intravenous corticosteroids, NSAIDs, and colchicine. However, negative effects have been linked with long term use of these drugs for symptomatic relief. In addition, patients are advised to restrict their diet, maintain their weight, and live a healthy lifestyle for better success from drug treatment.
Treatment options although available, are limited, and further exploration on the mechanisms behind gout pathogenesis will feed into the discovery of efficacious therapeutic drugs.
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