Xanthinuria, which was first described by Dent and Philpot in 1954, is characterized by excretion of large amounts of xanthine in the urine and a tendency to form xanthine stones. Uric acid is strikingly diminished in serum and urine. Two clinically similar but distinct forms of xanthinuria are recognized. In type I there is an isolated deficiency of xanthine dehydrogenase, and in type II there is a dual deficiency of xanthine dehydrogenase and aldehyde oxidase (603592). Type I patients can metabolize allopurinol, whereas type II patients cannot. Xanthinuria also occurs in molybdenum cofactor deficiency.
- Abdominal pain
- Joint pain
- Failure to thrive
- Flank pain
- Urinary tract infection
Ichida et al. studied 4 individuals with classic xanthinuria to discover the molecular cause of the enzyme deficiency. One subject had a C-to-T transition at nucleotide 682 of the XHD gene that caused an arg228-to-ter nonsense substitution (607633.0001). The duodenal mucosa from this subject had no xanthine dehydrogenase protein, while the mRNA level was not reduced. Two other subjects who were sibs were homozygous for this mutation, while another subject was found to carry the same mutation in heterozygous state. The fourth subject had a deletion of C at nucleotide 2567 in cDNA that was predicted to generate a termination codon from nucleotide 2783 (607633.0002). This subject was homozygous for the mutation and the level of mRNA in the duodenal mucosa was not reduced.
Beaudet indicated that the mutation in type II xanthinuria may not be in the structural gene for either xanthine dehydrogenase or aldehyde oxidase, but possibly in the mechanism responsible for inserting the essential sulfur atom into the active center of both enzymes.
The phrase "signs of Xanthinuria" should, strictly speaking, refer only to those signs and symptoms of Xanthinuria that are not readily apparent to the patient. The word "symptoms of Xanthinuria" is the more general meaning;