01At a glance
02What it is
Wilson disease is an autosomal recessive disorder of copper transport caused by ATP7B deficiency, leading to toxic copper accumulation in the liver, brain, and cornea. It presents with liver disease, neuropsychiatric symptoms, and Kayser-Fleischer rings. Treatment is copper chelation and zinc — removing the toxic metal, a strategy distinct from degradation or replacement.
03What goes wrong
Loss-of-function copper transporter leading to copper overload. ATP7B normally exports copper into bile; its deficiency causes copper to accumulate in the liver, brain, and cornea. The pathology is driven by the toxic copper overload (a downstream metal accumulation), not by a toxic protein aggregate and not by a simple enzyme-replaceable deficiency.
04How NIGHTINGALE routes it
Recommended modality: chelator (remove excess copper — penicillamine, trientine) + zinc (block absorption)
NOT eligible (protein-level). The disease is copper overload due to a loss-of-function transporter; the correct intervention is copper CHELATION (remove the toxic metal) or zinc therapy (block absorption), not protein degradation or enzyme replacement.
05Treatment today
D-Penicillamine and Trientine (chelators); Zinc acetate (absorption blocker)
Penicillamine/trientine/zinc long-established for Wilson diseaseChelators bind and promote urinary excretion of excess copper; zinc induces metallothionein to block intestinal copper absorption. Both lower body copper burden.
06In the pipeline
- Tetrathiomolybdate (investigational chelator)
- Gene therapy / hepatocyte transplantation (preclinical)
Key reference: PMID 10441329 · PubMed
07Verification
Every line below is the registry's own verification record — what was checked, against which source, and what is still open.
- uniprot: P35670 = ATP7B (Copper-transporting ATPase 2), 1465 aa — VERIFIED via UniProt REST API (live)
- gene mutation: ATP7B loss-of-function — VERIFIED (OMIM 277900)
- inheritance: Autosomal recessive — VERIFIED (OMIM 277900; Orphanet)
- orpha code: 905 = Wilson disease (Active) — VERIFIED via Orphanet API (live, 2026-07-02)
- drug mw: Chelators (penicillamine/trientine) + zinc — MWs not individually re-verified this session
- fda date: Copper chelation long-established — commonly cited
08Sources
| Fact | Source | Accession | Retrieved |
|---|---|---|---|
| Gene/protein identity | UniProt | P35670 (ATP7B, 1465 aa) | 2026-10-04 |
| Disease classification & definition | Orphanet | ORPHAcode 905 (Wilson disease) | 2026-10-04 |
| Inheritance & genetics | OMIM | 277900 (Wilson Disease) | 2026-10-04 |
Corrections carried into registry v2 (2)
- VERIFIED (2026-10-04): built fresh. ORPHAcode 905 confirmed live via Orphanet API.
- CLARIFIED: Wilson is a CHELATABLE METAL overload disease — the correct modality is copper CHELATION (remove the toxic metal), not protein degradation, not enzyme replacement, not a channel drug.