GOUT - A DISORDER OF PURINE NUCLEOTIDE METABOLISM

Introduction

Gout is a disorder of purine nucleotide metabolism. Cause joints to become red, tender and swollen. Also, may lead to kidney stones which cause kidney failure .Excessive production of uric acid leads to this condition (more than 7mg/dl). Further these uric acids get precipitated into mono sodium urate crystals which accumulate into joints and cause swelling and inflammation of joint. There are two types of gouts namely, primary gout and secondary gout.

Primary Gout: Due to defect in purine nucleotide metabolism

Secondary Gout:  Cancer, chemotherapy, psoriasis and renal dysfunction cause this condition. 

Signs and Symptoms

The most common signs of gout is inflammatory arthritis which is characterized by redness, tenderness and swelling of the affected joint. Usually, the first metatarso pharyngeal joint of great toe is affected (almost in 90% of the cases). As the uric acid levels rise the uric acid gets precipitated and form tophi which gets accumulated in joints.

Cause

There are several factors which are responsible for this condition to occur.

They are as follows:

• Genetics: We can consider gout as a genetic disorder, as in 60% of cases it's genetic. The ABCG2, SLC2A9 and SLC22A12 genes are commonly involved in gout and approximately double the risk.
• Medical Conditions: Gout generally occurs with severe other conditions like metabolic disorder, insulin resistance, increased lipid levels, obesity. (this occurs in nearly 58% of cases)
• Medications: Immunosuppressive drugs like tacrolimus and cyclosporine are involved in causing gout. Also drugs like aspirin, niacin, beta blockers, ACE inhibitors and ritonavir are associated in gout formation.
• Lifestyle: Intake of foods containing high amounts of purine like alcohol, organ meat, shrimps, mushrooms, seaweed cause gout. Physical trauma and surgery leads to increase level of purine in body. But purine rich vegetables are not associated in causing gout.

Diagnosis

Diagnostic methods include synovial fluid aspiration, blood test and differential diagnosis

Synovial Fluid Aspiration: A type of confirmatory test.

Blood Tests: Done for the assessment of uric acid levels. Usually WBC and ESR levels are increased in gout. Also the levels of uric acid is increased (more than 7 mg/dl)

Differential Diagnosis: Include studying of X-rays and mono sodium urate crystals under microscope. Gout resembles certain clinical conditions like rheumatoid arthritis, reactive arthritis and pseudo gout. So differential diagnosis plays a significant role in diagnosing gout.

Prevention

Change in lifestyle and medication can help to reduce the levels of uric acid. Preventing eating of foods of animal origin such as seafood, meat and alcohol reduces the levels of uric acid. Eating dairy products, intake of vitamin C, coffee and cherries prevent attacks of gout and help in reducing your body weight.

Medications

• Allopurinol: Allopurinol gets itself converted into alloxanthine, which is inhibitor of xanthine oxidase (enzyme required for synthesis of uric acid).This is an example of competitive inhibition
• Non-steroidal Anti Inflammatory Drug (NSAID): Helps in reducing pain and inflammation
• Alcohol: Alcohol gets converted into NADPH , which helps in conversion of mono sodium urate crystals into uric acid (excretable form)
• Febuxostat: Given to patients who cannot tolerate Allopurinol. Reduce uric acid levels more than Allopurinol.
• Probenecid: Less affective than Allopurinol, usually used in second line agent
• Lesinurad: Reduces blood uric acid levels by preventing uric acid absorption in the kidneys

Epidemiology

Every year 1-3% of western population gets affected by gout. In 2013 around 5.8 million people all around the globe were affected. From 1990-2010 the rates of gout have become doubled .Age, race and seasonal variations are the factors that promote the rate of gout. In comparison to European and African males, double the men’s are affected by gout in USA. Rates of gout are high in Pacific Islanders and least in Australians. Gout is a common condition in China, Polynesia, and urban sub-Saharan Africa. Most commonly the gout attacks occur in spring season.