Primary gout

Primary gout can be caused by overproduction of purine catabolites due to X-linked mutations of PRPP synthetases that render the enzyme insensitive to allosteric inhibitors. 

Estrogen is uricosuric and that is most probably the reason why premenopausal women do not have primary gout. Estrogen hormone replacement therapy in post-menopausal women lowered serum uric acid (SUA). Consequently, the prevalence of primary gout in these subjects is similar to what is seen in pre-menopausal women. 

Primary gout (hyperuricemia) is the form of the disease that is attributable to an inborn error of metabolism, such as overproduction of uric acid. 

Allopurinol is used to lower uric acid levels in the treatment of primary gout, as a prophylaxis in myeloproliferative neoplastic disease, for investigational purposes in Lesch-Nyhan syndrome, and as an adjunct with thiazide diuretics or ethambutol (see Chapter 24). Allopurinol acts by inhibiting xanthine oxidase, which converts hypoxanthine into xanthine and in turn becomes oxidized into uric acid. 

The most recent application of RPLC to the analysis of enzymes has been reported by Halfpenny and Brown (HI). An assay for purine nucleoside phosphorylase, a key mediator in the purine salvage pathway, has been developed and optimal conditions for the analysis determined. Figure 20 illustrates the simultaneous separation of the substrate, inosine, and products, uric acid and hypoxanthine. In another analysis. Halfpenny and Brown (H2) developed an assay for hypoxanthine-guanine phos-phoribosyltransferase. Deficiency of this enzyme has been associated with Lesch-Nyhan syndrome as well as primary gout. The activity of the enzyme is determined by measurement of the decrease of the substrate, hypoxanthine, and increase in the product, inosine-5 -monophosphoric acid. A major advantage of using HPLC for enzyme assays is that the simultaneous measurement of both substrate and product reduces the error due to interference from competing enzymes. 

Allopurinol (4-hydroxypyrazolo [3, 4-d] pyrimidine) is an inhibitor of xanthine oxidase that was successfully introduced in the treatment of primary gout about 45 years ago [171]. Allopurinol continues to be accepted as standard therapy in the treatment of primary and secondary hyperuricemia. Adverse reactions occur in about 10% of patients treated with allopurinol and are relatively mild and self-limited [171,172]. A mild maculopapular eruption or gastrointestinal disorders are usually noted, which promptly regress with cessation of therapy. Isolated instances of allopecia [173], bone marrow depression [174], ocular lesions [175], acute cholangitis [176], various types of hepatic injuries [177,178] temporal arthritis [179], and xanthine stones [180] have been reported. Recently, LaRosa et al [180a] have reported a case of xanthine nephropathy during treatment of childhood T-cell ALL. 

Primary gout is a disorder of purine metabolism seen predominantly in men. The condition is multifactorial and involves genetic and nongenetic factors. Occurrence in women is uncommon when it does occur, it is usually found in postmenopausal women. The blood urate concentration of normal men is 1 mg/dL higher than that in women, but this difference disappears after the menopause. Thus, in women, the postmenopausal rise in serum urate levels may increase the risk of developing gout. Gout is very rare in children and adolescents. 

W9. Wyngaarden, J. B., Normal glycine incorporation into uric acid in primary gout. Metah., Clin. Exptl. 7, 374-375 (1958). 

Gout is treated with diet and with several drugs. Dietary control (i.e., reduced consumption of food that is rich in nucleic acids such as liver and sardines) depresses uric acid synthesis in some individuals who are susceptible to primary gout. Allopurinol and colchicine are often used in gout therapy. Because allopurinol... 

Clinical features, which can enable lead gout to be differentiated from primary gout, have been described... 

Emmerson BT. The clinical differentiation of lead gout from primary gout. Arthritis Rheum 1968 11 623-624. 

Gout is a metabolic disease characterized by recurrent episodes of acute arthritis, usually monoarticular, and is associated with abnormal levels of uric acid in the body, particularly the presence of monosodium urate crystals in synovial fluid. Primary gout is a hereditary disease in which hyperuricemia is caused by an error in uric acid metabolism—either overproduction or an inability to excrete uric acid. Secondary gout refers to those cases in which hyperuricemia is caused by an acquired disease or disorder, such as chronic renal disease, lead poisoning, or myeloproliferative disorders. Gout generally occurs in... 

G7. Gutman, A. B., Views on the pathogensis and management of primary gout. J. Bone Joint Surg., Amer. Vol. 54, 357-372 (1972). 

A retrospective computer assisted analysis of 200 men with primary gout has heen carried out. Diagnosis was "based on clinical observations, X ray findings and laboratory data. ... 

Table 2. Percentage Distribution of Positive Responses Among Men with Primary Gout...

E. Wiedemann, H.G. Rose and E. Schwartz,. Plasma lipoproteins. Glucose Tolerance and Insulin response in Primary Gout. Amer. J. 

Lipoprotein abnormalities are common in gout. The most frequent is hypertriglyceridemia, which has been reported in three-quarters of patients with primary gout (1, 2). This alteration may or may not be related to obesity, alcohol consumption, and glucose intolerance (3). Patients with gout secondary to lead nephropathy do not have hypertriglyceridemia (4). 

To investigate these new aspects of lipoprotein metabolism in primary gout, we studied a group of 32 patients and a group of 32 controls comparable in age and body weight, but with normal serum uric acid. 

Table I. Behavior of Various Parameters in 32 Controls (A) and in 32 Patients with Primary Gout (B)...

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