NeurometPlus

Incidence

Xanthine dehydrogenase deficiency has been identified in more than 100 cases, both male and female, of caucasian, Asian, oriental and negroid descent. Studies in several kindreds are consistent with an autosomal recessive mode of inheritance. There is a strong element of consanguinity in cases presenting with the combined defect.

Clinical Characteristics

Two clinically similar but distinct forms of xanthinuria are recognized. In type I xanthinuria, there is an isolated deficiency of xanthine dehydrogenase; in type II, there is a dual deficiency of xanthine dehydrogenase and aldehyde oxidase. Type I patients can metabolize allopurinol, whereas type II patients cannot. The combined deficiency of XDH and aldehyde oxidase might be relatively common. Since the molybdenum cofactor is also required for aldehyde oxidase, patients with the combined defect are likewise aldehyde oxidase deficient. The defect may generally by identified by the low to undetectable concentrations of uric acid in plasma. On a purine-free diet uric acid is virtually undetectable in plasma or urine, being replaced by xanthine and to a lesser extent hypoxanthine, with an approximate ratio in urine of 4-5:1. Classical xanthinuria has two types - an isolated deficiency (XDH type I), a dual deficiency with aldehyde oxidase (XDH/AOX: type II). Additionally xanthiuria occurs in Molybdenum cofactor deficiency, where sulphite oxidase (SO) is also inactive. More than 150 cases of both types have been described from 22 countries, indicating that the disorder is not confined to specific ethnic groups. Although xanthinuria is a rare disorder the number of cases found is certainly an underestimate. Clinical symptoms in classical XDH deficiency include xanthine calculi, crystalluria, or acute renal failure and unrecognized can lead to end-stage renal disease, nephrectomy, or death. All symptoms relate to the extreme insolubility and high renal clearance of xanthine and can manifest from birth to the 80's, 50% of cases being children. Duodenal ulcers, myopathy, or arthropathy have been noted in 10%. Treatment involves high fluid intake and dietary purine restriction. Twenty percent of type 1 and 2 patients (and occasional cofactor patients), have been asymptomatic.

Precipitants

Dehydration and hot weather may precipitate renal crisis.

Provocation Tests

None.

Diagnostic Procedures

The defect may generally by identified by the low to undetectable concentrations of uric acid in plasma. On a purine-free diet uric acid is virtually undetectable in plasma or urine, being replaced by xanthine and to a lesser extent hypoxanthine, with an approximate ratio in urine of 4-5:1.