Pompe Disease (Glycogen Storage Disease Type II) — NEXUS NIGHTINGALE disease dossier

01At a glance

Gene

GAA

Protein

Lysosomal alpha-glucosidase (acid maltase / alglucosidase alfa)UniProt P10253 · 952 aa

Inheritance

Autosomal recessive — GAA mutations

Age of onset

Infantile onset (0-12 months, severe cardiomyopathy) or late-onset (childhood/adult, muscle weakness)

Prevalence

~1 in 40,000 (all forms combined); infantile form ~1 in 138,000 — commonly cited; UNVERIFIED exact figure this sessionMarked unverified in the registry

02What it is

Pompe disease is an autosomal recessive lysosomal storage disorder caused by acid alpha-glucosidase (GAA) deficiency, leading to glycogen accumulation in muscle. The infantile form causes severe cardiomyopathy and early death; the late-onset form causes progressive muscle weakness and respiratory failure. Enzyme replacement therapy is the standard disease-modifying treatment.

03What goes wrong

Loss-of-function. Deficiency of lysosomal alpha-glucosidase (acid maltase) impairs lysosomal glycogen degradation, causing glycogen to accumulate in lysosomes, especially in skeletal and cardiac muscle. This causes progressive muscle weakness, respiratory failure, and (in the infantile form) severe hypertrophic cardiomyopathy.

04How NIGHTINGALE routes it

mechanism: enzyme_lof not a degradation target

Recommended modality: enzyme replacement therapy (approved)

NOT eligible. Pompe disease is a loss-of-function enzyme deficiency — acid alpha-glucosidase is deficient, not accumulated. Correct route is enzyme replacement therapy (restore GAA), not protein degradation.

05Treatment today

Alglucosidase alfa (Myozyme/Lumizyme)

2006 (Myozyme, infantile-onset); 2010 (Lumizyme, late-onset)

Enzyme replacement therapy (recombinant acid alpha-glucosidase) · biologic — MW not applicable

Recombinant acid alpha-glucosidase that replaces the deficient enzyme, restoring lysosomal glycogen degradation. Administered intravenously every 2 weeks. Disease-modifying for both infantile and late-onset forms.

06In the pipeline

Next-generation ERT: avalglucosidase alfa (Nexviazyme) — improved M6P targeting
Cipaglucosidase alfa + miglustat (two-component ERT, Pombiliti+Opfolda)
Gene therapy (AAV-mediated GAA delivery, clinical)

Key reference: PMID 18429042 · PubMed

07Verification

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

uniprot: P10253 = GAA (Lysosomal alpha-glucosidase), 952 aa — VERIFIED via UniProt REST API (live)
gene mutation: GAA loss-of-function mutations — VERIFIED (OMIM 232300)
inheritance: Autosomal recessive — VERIFIED (OMIM 232300; Orphanet ORPHAcode 365)
orpha code: 365 = Glycogen storage disease due to acid maltase deficiency (Active) — VERIFIED via Orphanet API (live, 2026-07-02)
drug mw: Alglucosidase alfa is a recombinant enzyme (~110 kDa), not a small molecule — MW/CID NOT APPLICABLE (left 0, not fabricated)
fda date: Myozyme 2006 / Lumizyme 2010 — 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	P10253 (GAA, Lysosomal alpha-glucosidase, 952 aa)	2026-10-04
Disease classification & definition	Orphanet	ORPHAcode 365 (Glycogen storage disease due to acid maltase deficiency)	2026-10-04
Inheritance & genetics	OMIM	232300 (Glycogen Storage Disease II / Pompe Disease)	2026-10-04

Source record: ORPHAN-008.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 365 confirmed live via Orphanet API (preferred term is 'Glycogen storage disease due to acid maltase deficiency', not 'Pompe').
CLARIFIED: alglucosidase alfa is a recombinant enzyme (not a small molecule), so MW/PubChem CID are intentionally 0.
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.