Disorders of Purine metabolism. Gout

Question 1

General information

Answer 1

Abnormalities in the biosynthesis, interconversion and degradation of the purines (adenine and guanine). Gout is the most common human disease related to purine metabolism. It occurs due to excess amounts of uric acid, which is the end product of purine metabolism.

The excess can either be due to overproduction or reduced excretion.

Question 2

Risk factors

Answer 2

Male sex, obesity, excess alcohol intake, consumption of purine-rich food, diabetes, metabolic syndrome and renal failure.

Question 3

Pathomechanism

Answer 3

Monosodium urate crystals precipitate from supersaturated body fluids and induce an acute inflammation.

Question 4

Manifestation of Gout

Answer 4

Acute arthritis, with crystals in cytoplasm of neutrophils and in the synovium.
Chronic tophaceous arthritis: after repeated attacks the joints may deform
Tophi: formation of large crystalline aggregates, which can appear in tendons, soft tissues and articular cartilage (Surrounded by macrophages, lymphocytes and foreign-body giant cells).
Gouty nephropathy: Renal complications due to urate deposition, involving glomerular, tubular and interstitial tissues and blood vessels. Hypertension and urolithiasis is common.

Question 5

Primary gout

Answer 5

Idiopathic, occurs due to excessive uric acid biosynthesis. Rarely a congenital metabolic defect, like a complete lack if HGPRT (hypoxanthine-guanine phosphoribosyl transferase). It is an enzyme which is essential in the salvage pathway. Gives rise to the X-linked Lesch-Nyhan syndrome

Question 6

Secondary gout

Answer 6

Can be due to:
Polycythemia vera and other myeloproliferative disorders
Cytotoxic treatment of malignant disease
Diuretic treatment
Low dose aspirin treatment
Chronic renal failure
Psoriasis
Hemolytic anemias
Lead nephropathy

Question 7

Diagnosis of Gout

Answer 7

Characteristic asymmetric oligoarthitis
Monosodium urate crystals in the synovial fluid
Rapid response of pain and inflammation when administrating colhicin. The effect of the drug is specific for gout.

Question 8

Treatment of gout

Answer 8

Acute:
Administer 0.5mg of Colihicin hourly, maximal dose is 4-8mg due to GI side effects.
High dose of NSAIDs
Steroids

Chronic:
Diet
Allopurinol
Probenecid, sulfinpyrazon, benzbromaron
Alkalization of urine, increased fluid intake
Chronic Colhicin treatment: 0.5-1mg/day

Question 9

Other diseases of purine metabolism

Answer 9

ADA and PNP deficiencies which lead to lymphopenia and immunodeficiency