Fabry Disease — NEXUS NIGHTINGALE disease dossier

01At a glance

Gene

GLA

Protein

Alpha-galactosidase A (agalsidase)UniProt P06280 · 429 aa

Inheritance

X-linked — GLA mutations (Î±-galactosidase A deficiency)

Age of onset

Childhood (neuropathic pain, angiokeratomas); renal/cardiac complications in adulthood

Prevalence

~1 in 40,000-60,000 males (classic form); higher in some populations — commonly cited; UNVERIFIED exact figure this sessionMarked unverified in the registry

02What it is

Fabry disease is an X-linked lysosomal storage disorder caused by Î±-galactosidase A deficiency, leading to globotriaosylceramide accumulation in the kidneys, heart, and vasculature. It causes progressive renal failure, cardiomyopathy, and neuropathic pain. Enzyme replacement and chaperone therapy are the standard disease-modifying approaches.

03What goes wrong

Loss-of-function. Deficiency of Î±-galactosidase A (GLA) impairs lysosomal degradation of globotriaosylceramide (Gb3), which accumulates in vascular endothelium, kidneys, heart, and nervous system. This causes progressive renal failure, cardiomyopathy, neuropathic pain, and cerebrovascular events.

04How NIGHTINGALE routes it

mechanism: enzyme_lof not a degradation target

Recommended modality: enzyme replacement therapy + chaperone (approved)

NOT eligible. Fabry disease is a loss-of-function enzyme deficiency — GLA is deficient, not accumulated. Degrading residual enzyme would worsen the disease. Correct route is enzyme replacement therapy (restore GLA) or chaperone therapy, not protein degradation.

05Treatment today

Agalsidase beta (Fabrazyme)

2003 (Fabrazyme)

Enzyme replacement therapy (recombinant Î±-galactosidase A) · biologic — MW not applicable

Recombinant Î±-galactosidase A that replaces the deficient enzyme, restoring Gb3 degradation. Administered intravenously every 2 weeks. Disease-modifying for the non-classic and classic forms.

06In the pipeline

Pharmacological chaperone therapy: migalastat (Galafold) — oral, for amenable GLA mutations
Substrate reduction therapy (investigational)
Gene therapy (AAV-mediated GLA delivery, clinical)

Key reference: PMID 26415523 · PubMed

07Verification

Every line below is the registry's own verification record — what was checked, against which source, and what is still open.

uniprot: P06280 = GLA (Alpha-galactosidase A), 429 aa — VERIFIED via UniProt REST API (live)
gene mutation: GLA loss-of-function mutations — VERIFIED (PMC7918333: Fabry Disease Molecular Basis)
inheritance: X-linked — VERIFIED (OMIM 301500; Orphanet)
orpha code: 324 = Fabry disease (Active) — VERIFIED via Orphanet API (live, 2026-07-02)
drug mw: Agalsidase beta is a recombinant enzyme (~100 kDa), not a small molecule — MW/CID NOT APPLICABLE (left 0, not fabricated)
fda date: Fabrazyme (agalsidase beta) 2003 — commonly cited; exact NDA not re-verified this session

Amber entries are the registry's own open items — figures it could not re-confirm in the 2026-10-04 pass. They are shown rather than hidden.

08Sources

Fact	Source	Accession	Retrieved
Gene/protein identity	UniProt	P06280 (GLA, Alpha-galactosidase A, 429 aa)	2026-10-04
Disease classification & definition	Orphanet	ORPHAcode 324 (Fabry disease)	2026-10-04
Inheritance & genetics	OMIM	301500 (Fabry Disease)	2026-10-04
Disease mechanism & therapy	PMC	PMC9967779 (Treatment of Fabry Disease: Established and Emerging Therapies)	2026-10-04

Source record: ORPHAN-007.json — orphan registry v2.0-fresh-2026-10-04. Protocol: TJ Compassion + L.O.V.E. — every fact live-verified against UniProt / PubChem / ClinVar / OMIM / FDA / Orphanet

Fresh orphan registry entry built 2026-10-04 under the orphan-disease-verification skill.

Corrections carried into registry v2 (3)

VERIFIED (2026-10-04): built fresh. ORPHAcode 324 confirmed live via Orphanet API.
CLARIFIED: agalsidase beta is a recombinant enzyme (not a small molecule), so MW/PubChem CID are intentionally 0.
CLARIFIED: enzyme replacement / chaperone therapy is the correct route for a LoF lysosomal storage disease — NOT AUTOTAC.

09Scope and limits

This page is a research summary for teaching and scientific communication. It is not medical advice, a diagnosis, or a treatment recommendation. NEXUS NIGHTINGALE is a computational research pipeline; it is not clinically validated and none of its output has regulatory approval. Prevalence and approval figures marked unverified must be confirmed against the cited source before external use.