| Domain | Type I | Type II | Evidence/notes |
|---|---|---|---|
| Causal gene | **XDH** | **MOCOS** | Biallelic loss-of-function variants cause classical hereditary xanthinuria (pqac-00000007, pqac-00000008) |
| OMIM disease ID | **278300** | **603592** | Current genetic-nephrolithiasis review confirms both subtype mappings (pqac-00000015) |
| Inheritance | Autosomal recessive | Autosomal recessive | Consanguinity, homozygosity, and founder effects are frequent in reported families (pqac-00000001) |
| Enzyme defect | Isolated xanthine dehydrogenase/xanthine oxidoreductase deficiency | Combined xanthine dehydrogenase/xanthine oxidoreductase and aldehyde oxidase deficiency | MOCOS normally sulfurates molybdenum cofactor required by both enzymes (pqac-00000007, pqac-00000010) |
| Core biomarkers | Profound hypouricemia and hypouricosuria; increased urinary xanthine and hypoxanthine | Same core biochemical profile | Fractional urate excretion is generally normal or low; one type I case had serum urate <5.95 µmol/L and combined urinary xanthine/hypoxanthine of 108.35 µmol/mmol creatinine (pqac-00000021) |
| Principal complications | Xanthine crystalluria and radiolucent urolithiasis; obstruction, hematuria, renal colic, urinary infection, hydronephrosis, and rarely kidney failure; occasional myopathy/arthropathy | Similar renal and extra-renal phenotype, plus potential toxicity from drugs dependent on aldehyde oxidase metabolism | Approximately 35% of a 20-patient cohort were symptomatic; historical series suggest stones or attributable symptoms in roughly 40% (pqac-00000000, pqac-00000001, pqac-00000020) |
| Diagnostic confirmation | Biallelic pathogenic/likely pathogenic **XDH** variants | Biallelic pathogenic/likely pathogenic **MOCOS** variants; aldehyde-oxidase functional/metabolite testing can distinguish type II | Confirm biochemical suspicion with sequencing that covers coding regions, splice boundaries, and copy-number changes; historical allopurinol loading is now secondary to molecular testing (pqac-00000019, pqac-00000022) |
| Management | High fluid intake; low-purine diet; reduce purine- and fructose-rich foods; monitor renal function and stone burden; remove obstructing stones when necessary | Same measures, with added medication review for aldehyde-oxidase-dependent drugs | No disease-specific pharmacotherapy is established. Urine alkalinization has uncertain or little benefit because xanthine solubility is relatively pH-independent; allopurinol is not routine therapy and may increase xanthine burden (pqac-00000019, pqac-00000022, pqac-00000024) |


*Table: Compact comparison of the genetic, biochemical, clinical, diagnostic, and management features of hereditary xanthinuria types I and II. Evidence notes identify established findings and important treatment cautions.*