- What Causes Over-Production Of Urate?
- What Causes Under-Excretion?
- What Is The Role Of Kidney Disease?
- Do Diet And Alcohol Have Any Influence?
- Are Other Health Factors Important?
In every patient with gout, a variety of factors contribute to the hyperuricaemia, and different factors contribute in different degrees in different patients. Thus, excessive production of urate will cause hyperuricaemia unless it is compensated by a corresponding increase in the excretion ofurate. Alternatively, reduced excretion of urate will cause hyperuricaemia unless there is a compensatory reduction in urate production.
An increase in urate production is sometimes referred to as over-production of urate, and a reduced excretory capacity for urate is sometimes referred to as under-excretion of urate. These are the two major mechanisms which result in hyperuricaemia.
While both over-production and under-excretion of urate can result in hyperuricaemia, each may be modified by both genetic and acquired (environmental) factors.
Genetic Over-Production Of Urate
The major enzyme which, when defective, causes gross over-production of urate is called HPRT (hypoxanthine phosphoribosyi transferase). The gene or code for this enzyme is located on the X chromosome, and because of this, any defect in this HPRT gene shows up only in males and is transmitted by a female carrier who is herself normal or only very mildly affected. (Females have two X chromosomes, one from each parent, and both copies would have to be faulty for the defect to show up. Males have one X chromosome, from the mother, and a Y chromosome, from the father.
This means that there is nothing to correct any errors on their X chromosome. Most defects transmitted on the X chromosome therefore only show up in males.) Thus a man with HPRT deficiency would show urate over-production and might pass on the gene to his daughter. She would not usually develop symptoms, but could, transmit the deficiency to her sons.
Although the enzyme deficiency itself is relatively rare, these enzyme mutations can sometimes arise spontaneously and there may be no other members of the family affected. There are about twelve families in Australia known to have this HPRT mutation leading to over-production of urate, but these families include many hundreds of people. There are other rare mutations affecting urate production but they are even less common than the HPRT mutation.