MOCOS – Xanthinuria Type II

Patients with autosomal recessive xanthinuria type II present with profound hypouricemia, elevated plasma oxypurines and undetectable xanthine dehydrogenase/oxidase (XDH/XO) activity. Two unrelated adult females were diagnosed with xanthinuria type II on the basis of biochemical profiling and genetic testing in MOCOS and Xanthinuria type II. The first proband was homozygous for c.169G>C (p.Ala57Pro) (PMID:14624414), and the second carried a homozygous c.362C>T (p.Thr121Met) variant (PMID:29935280). Both variants are predicted to disrupt molybdenum cofactor sulfurase function and segregate with disease in a recessive pattern.

Enzymatic assays confirm a loss‐of‐function mechanism: duodenal mucosa from the first patient had XDH/XO activity below detection limits, and plasma from the second showed <2% of control activity (PMID:29935280). These data establish that biallelic MOCOS missense variants abrogate enzyme function, leading to systemic accumulation of xanthine and hypouricemia. Genetic testing for MOCOS should be considered in individuals with unexplained hypouricemia and high oxypurine levels.

References

• Metabolism: clinical and experimental • 2003 • Identification of a new point mutation in the human molybdenum cofactor sulferase gene that is responsible for xanthinuria type II. PMID:14624414
• Toxicology and applied pharmacology • 2018 • Thiopurine-induced toxicity is associated with dysfunction variant of the human molybdenum cofactor sulfurase gene (xanthinuria type II). PMID:29935280

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