Gout and its types

  • Gout is a metabolic disease which is associated with overproduction of uric acid.
  • Uric acid is found in a more soluble form as sodium urate at the physiological pH.
  • Crystals of sodium urate get deposited in the soft tissues particularly in the joints in case of severe hyperuricemia.
  • Such deposits are commonly called tophi.
  • This leads to inflammation in the joints resulting in a painful gouty arthritis.
  • Sodium urate or uric acid may also precipitate in kidney and ureters that result in renal damage and stone formation.
  • Gout was found to be often associated with high living, over-eating and alcohol consumption.
  • In the previous centuries, alcohol was contaminated with lead during its manufacture and storage.
  • Lead poisoning leads to kidney damage and decreased uric acid excretion causing gout.
  • The prevalence of gout is 3 per 1000 persons, mostly affecting males.
  • Post-menopausal women are as susceptible as men for this disease.
  • Gout is of two types. They are:

A)Primary Gout

  • It is an inborn error of metabolism due to overproduction of uric acid.
  • This is mostly related to increased synthesis of purine nucleotides.
  • The following are the important metabolic defects associated with primary gout.

i)PRPP synthetase

  • In normal circumstances, PRPP synthetase is under feedback control by purine nucleotides ADP and GDP.
  • However, variant forms of PRPP synthetase which are not subjected to feedback regulation have been detected.
  • This leads to increased production of purines.


ii)PRPP glutamyl-amido-transferase

  • There is lack of feedback control of this enzyme by purine nucleotides which also leads to their elevated synthesis.


iii)HGPRT deficiency

  • This is an enzyme of purine salvage pathway which defect causes Lesch-Nyhan syndrome.
  • This disorder increases the synthesis of purine nucleotides by a two-fold mechanism.
  • Firstly, decreased utilization of purines (hypoxanthine and guanine) by salvage pathway, resulting in the accumulation and diversion of PRPP for purine nucleotides.
  • Secondly, the defect in salvage pathway leads to decreased levels of IMP and GMP causing impairment in the tightly controlled feedback regulation of their production.

gouty arthritisको लागि तस्बिर परिणाम          सम्बन्धित छवि


iv)Glucose 6-phosphatase deficiency

  • In type I glycogen storage disease (von- Gierke’s), glucose 6-phosphate cannot be converted to glucose due to the deficiency of glucose 6-phosphatase.
  • This leads to the increased utilization of glucose 6-phosphate by hexose-monophosphate shunt (HMP shunt) resulting in the elevated levels of ribose 5-phosphate and PRPP.
  • This ultimately leads to purine overproduction.
  • von-Gierke’s disease is also associated with increased activity of glycolysis.
  • Due to this, lactic acid accumulates in the body which interferes with the uric acid excretion through renal tubules.


v)Elevation of glutathione reductase

  • Increased glutathione reductase generates more NADP+ which is utilized by HMP shunt.
  • This causes increased ribose 5-phospahte and PRPP synthesis.
  • Among the five enzymes described, the first three are directly involved in purine synthesis.
  • The remaining two indirectly regulate purine production.
  • This is a good example to show how an abnormality in one metabolic pathway influences the other.

gouty arthritisको लागि तस्बिर परिणाम   gouty arthritisको लागि तस्बिर परिणाम

B)Secondary gout

  • Secondary hyperuricemia is due to various diseases causing increased synthesis or decreased excretion of uric acid.
  • Increased degradation of nucleic acids (hence more uric acid formation) is observed in various cancers (leukemias, polycythemia, lymphomas, etc.), psoriasis and increased tissue breakdown (trauma, starvation, etc.).
  • The disorders associated with impairment in renal function cause accumulation of uric acid which may lead to gout.


i) https://www.versusarthritis.org/about-arthritis/conditions/gout/

ii) https://my.clevelandclinic.org/health/diseases/4755-gout

Gout and its types