Gout Phosphoribosyl transferase

EXAMPLE 14.13 In some diseases, excessive amounts of purines are produced in the body, leading to accumulation of urate. Patients with Lesch-Nyhan syndrome lack the enzyme hypoxanthine-guanine phosphoribosyl-transferase (HG-PRTase). Children born with this disorder are mentally retarded and prone to self-mutilation. They produce excessive amounts of purines due to accumulation of P-Rib-PP which stimulates the first enzyme of the purine synthesis pathway, amido PRTase (Fig. 14-18). Patients with Lesch-Nyhan syndrome may also suffer from gout, which is due to an accumulation of urate in the body with deposition of crystals of sodium urate in the joints and kidneys, or due to accumulation of P-Rib-PP for reasons other than a deficiency of HG-PRTase. 

The biochemical mechanism regulating the balance between de novo and salvage pathways remains to be discovered. But observation of patients afflicted with gout or the Lesch-Nyhan syndrome suggests that hypoxanthine guanine phosphoribosyl transferase may play an important role in maintaining the balance between de novo and salvage pathways. 

A form of hyperuricemia has been described which results from the partial deficiency of phosphoribosyl transferase. In this type of gout, the deficiency appears to result from the elaboration of an abnormal molecular form of the enzyme. Thus, the enzyme has been shown to alter electrophoretic properties and heat stabilities. 

Some rare inherited deficiencies of the purine-salvage enzymes hypoxanthine-phosphoribosyl-transferase (HPRT) and adenine-PRT (APRT) lead to primary purine overproduction (Table 20.5). X-linked Lesch-Nyhan syndrome occurs in complete deficiency of HPRT. It is characterized by mental retardation, self-mutilation, choreoathetosis, gout. 

Hypoxanthine - Guanine phosphoribosyl transferase deficiency in gout ... 

GOUT WITH ADENINE PHOSPHORIBOSYL TRANSFERASE DEFICIENCY... 

A systematic study of purine phosphoribosyl transferases has led to the discovery of a deficiency of adenine phosphoribosyl transferase (APRT) in a patient with gout and several members of his family, who were either suffering from gout, hyperuricaemia or were normal. 

If these metabolic disorders are considered to be related, then the cases of gout observed in this family are different in their manifestations to those resulting from a deficiency of hypo-xanthine guanine phosphoribosyl transferase (4). They are characterised by a slow onset, few clinical signs and especially absence of tophi and a remarkable effect of alio- and thiopurinol. 

As yet there is no firm evidence to suppose the hyperproduction of uric acid in the propositus is the result of deficiency of APRT and a raised feed back. Although this may be the mechanism in the case of gout associated with a hypoxanthine guanine phosphoribosyl transferase deficiency. 

Screening the purine phosphoribosyl transferases in patients with gout has demonstrated an adenine phosphoribosyl transferase deficiency in one of them. 

Further Evaluation of adenine phosphoribosyl transferase deficiency in man. Occurence in a patient with gout. 

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See also in sourсe #XX -- [ ]

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