Gaucher Disease — NEXUS NIGHTINGALE disease dossier

01At a glance

Gene

GBA1

Protein

Lysosomal acid glucosylceramidase (GCase / glucocerebrosidase)UniProt P04062 · 536 aa

Inheritance

Autosomal recessive — GBA1 mutations

Age of onset

Type 1: variable, childhood to adulthood; Type 2: infancy (severe); Type 3: childhood (neuronopathic)

Prevalence

~1 in 40,000-60,000 general population; ~1 in 850 in Ashkenazi Jewish population (commonly cited) — UNVERIFIED exact figure this sessionMarked unverified in the registry

02What it is

Gaucher disease is the most common lysosomal storage disorder, an autosomal recessive deficiency of glucocerebrosidase. It causes glucocerebroside accumulation in macrophages, leading to enlarged spleen/liver, low blood counts, and bone disease. Enzyme replacement therapy is the standard disease-modifying treatment for the non-neuronopathic form.

03What goes wrong

Loss-of-function. Deficiency of glucocerebrosidase (GCase) impairs lysosomal degradation of glucosylceramide, which accumulates in macrophages, forming 'Gaucher cells' in spleen, liver, and bone marrow. This causes hepatosplenomegaly, cytopenias, and bone disease (type 1, non-neuronopathic) or additional neurological involvement (types 2-3).

04How NIGHTINGALE routes it

mechanism: enzyme_lof not a degradation target

Recommended modality: enzyme replacement therapy (approved)

NOT eligible. Gaucher disease is a loss-of-function enzyme deficiency — GCase is deficient, not accumulated. The correct route is enzyme replacement therapy (restore GCase), not protein degradation.

05Treatment today

Imiglucerase (Cerezyme)

1994 (Cerezyme)

Enzyme replacement therapy (recombinant GCase) · biologic — MW not applicable

Recombinant human glucocerebrosidase that replaces the deficient enzyme, restoring glucosylceramide degradation. Administered intravenously. This is the definitive disease-modifying therapy for type 1 Gaucher disease.

06In the pipeline

Substrate reduction therapy: eliglustat (oral, glucosylceramide synthase inhibitor) and miglustat
Gene therapy (AAV-mediated GBA1 delivery, preclinical/early clinical)
Pharmacological chaperones (ambroxol, repurposed)

Key reference: PMID 28218669 · PubMed

07Verification

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

uniprot: P04062 = GBA1 (Lysosomal acid glucosylceramidase/GCase), 536 aa — VERIFIED via UniProt REST API (live)
gene mutation: GBA1 loss-of-function mutations — VERIFIED (GeneReviews NBK1269; StatPearls)
inheritance: Autosomal recessive — VERIFIED (OMIM 230800; Orphanet)
orpha code: 355 = Gaucher disease (Active) — VERIFIED via Orphanet API (live, 2026-07-02)
drug mw: Imiglucerase is a recombinant enzyme (~55 kDa), not a small molecule — MW/CID NOT APPLICABLE (left 0, not fabricated)
fda date: Cerezyme (imiglucerase) 1994 — 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	P04062 (GBA1, Lysosomal acid glucosylceramidase/GCase, 536 aa)	2026-10-04
Disease classification & definition	Orphanet	ORPHAcode 355 (Gaucher disease)	2026-10-04
Inheritance & genetics	OMIM	230800 (Gaucher Disease)	2026-10-04
Disease mechanism & therapy	GeneReviews	NBK1269 (Gaucher Disease)	2026-10-04

Source record: ORPHAN-006.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.

Corrections carried into registry v2 (3)

VERIFIED (2026-10-04): built fresh. ORPHAcode 355 confirmed live via Orphanet API.
CLARIFIED: imiglucerase is a recombinant enzyme (not a small molecule), so MW/PubChem CID are intentionally marked 0 rather than fabricating a small-molecule weight.
CLARIFIED: enzyme replacement therapy is the correct disease-modifying 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.