LATE-ONSET POMPE DISEASE AND CEREBROVASCULAR MANIFESTATIONS

NCT07685314 | Completed

• 1 other identifier: SGZ-2017-11891
• Study Type: observational
• Target: 477
• Locations: 1 country
• Sites: 1

Brief Summary

Late-onset Pompe disease (LOPD) is an inherited metabolic disorder caused by deficiency of acid alpha-glucosidase (GAA). In addition to skeletal and respiratory muscle involvement, previous studies suggest that patients with LOPD may have an increased frequency of cerebrovascular and aortic vascular abnormalities, but available evidence is limited. This multicenter, non-interventional study aims to determine whether pathogenic GAA mutations are associated with severe cerebrovascular or aortic vascular malformations. The study will include patients with confirmed LOPD and patients with intracranial aneurysms or subarachnoid hemorrhage. Clinical, laboratory, genetic, and imaging data will be collected to evaluate the frequency and characteristics of vascular abnormalities in LOPD and to identify previously undiagnosed cases presenting with vascular disease.

Conditions

Late-Onset Pompe Disease

Keywords

Late-Onset Pompe Disease; Glycogen Storage Disease Type II; Acid Alpha-Glucosidase Deficiency

Outcome Measures

Primary Outcomes (1)

• Prevalence of severe cerebrovascular and aortic vascular malformations in late-onset Pompe disease

  To determine the prevalence and characteristics of severe cerebrovascular and aortic vascular abnormalities in participants with genetically confirmed late-onset Pompe disease and to evaluate the association between pathogenic GAA mutations and vascular involvement.

  Baseline (at study assessment)

Secondary Outcomes (3)

• Frequency of reduced GAA enzyme activity in participants with intracranial aneurysm or subarachnoid hemorrhage

  Baseline

• Frequency and distribution of vascular malformations in late-onset Pompe disease

  Baseline

• Severity of vascular lesions

  Baseline

Study Arms (2)

Late-Onset Pompe Disease

Participants with genetically confirmed late-onset Pompe disease (LOPD). Clinical, laboratory, genetic, and vascular imaging data are collected to determine the prevalence and characteristics of cerebrovascular and aortic vascular abnormalities.

Intracranial Aneurysm/Subarachnoid Hemorrhage

Participants with intracranial aneurysm (ruptured or unruptured) and/or subarachnoid hemorrhage. Dried blood spot testing for acid alpha-glucosidase (GAA) activity is performed to identify previously undiagnosed late-onset Pompe disease, with confirmatory GAA gene sequencing in participants with reduced enzyme activity.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study includes two adult cohorts recruited in Spain: (1) patients with documented late-onset Pompe disease (LOPD) recruited through Spanish Neuromuscular Reference Units (CSUR), and (2) patients with ruptured or unruptured intracranial aneurysms or subarachnoid hemorrhage recruited from Interventional Neuroradiology Units. Participants are enrolled after providing informed consent and undergo clinical, imaging, and enzymatic evaluation to investigate the prevalence and spectrum of vascular abnormalities associated with late-onset Pompe disease.

You may qualify if:

• Adults aged 18 years or older.
• Written informed consent provided.
• Documented diagnosis of late-onset Pompe disease (LOPD), or patients with ruptured or unruptured intracranial aneurysm or subarachnoid hemorrhage (with or without an associated aneurysm).
• Willing and able to comply with study procedures and possessing adequate cognitive ability.

You may not qualify if:

• Participants unwilling or unable to comply with study procedures or lacking the cognitive ability required to participate

Sponsors & Collaborators

• Hospitales Universitarios Virgen del Rocío: lead
• Sanofi: collaborator

Study Sites (1)

Hospital Universitario Virgen del Rocío

Seville, 41013, Spain

Location

Related Publications (9)

• Montagnese F, Granata F, Musumeci O, Rodolico C, Mondello S, Barca E, Cucinotta M, Ciranni A, Longo M, Toscano A. Intracranial arterial abnormalities in patients with late onset Pompe disease (LOPD). J Inherit Metab Dis. 2016 May;39(3):391-398. doi: 10.1007/s10545-015-9913-x. Epub 2016 Feb 1.

  PMID: 26830551 BACKGROUND

• Garibaldi M, Sacconi S, Antonini G, Desnuelle C. Long term follow-up of cerebrovascular abnormalities in late onset Pompe disease (LOPD). J Neurol. 2017 Mar;264(3):589-590. doi: 10.1007/s00415-017-8396-0. Epub 2017 Jan 24. No abstract available.

  PMID: 28120044 BACKGROUND

• Wens SC, Kuperus E, Mattace-Raso FU, Kruijshaar ME, Brusse E, van Montfort KC, de Boer MS, Sijbrands EJ, van der Ploeg AT, van Doorn PA. Increased aortic stiffness and blood pressure in non-classic Pompe disease. J Inherit Metab Dis. 2014 May;37(3):391-7. doi: 10.1007/s10545-013-9667-2. Epub 2014 Jan 10.

  PMID: 24407465 BACKGROUND

• El-Gharbawy AH, Bhat G, Murillo JE, Thurberg BL, Kampmann C, Mengel KE, Kishnani PS. Expanding the clinical spectrum of late-onset Pompe disease: dilated arteriopathy involving the thoracic aorta, a novel vascular phenotype uncovered. Mol Genet Metab. 2011 Aug;103(4):362-6. doi: 10.1016/j.ymgme.2011.04.009. Epub 2011 May 5.

  PMID: 21605996 BACKGROUND

• Hensel O, Hanisch F, Stock K, Stoevesandt D, Deschauer M, Muller T. Morphology and function of cerebral arteries in adults with pompe disease. JIMD Rep. 2015;20:27-33. doi: 10.1007/8904_2014_385. Epub 2015 Jan 23.

  PMID: 25614309 BACKGROUND

• Anneser JM, Pongratz DE, Podskarbi T, Shin YS, Schoser BG. Mutations in the acid alpha-glucosidase gene (M. Pompe) in a patient with an unusual phenotype. Neurology. 2005 Jan 25;64(2):368-70. doi: 10.1212/01.WNL.0000149528.95362.20.

  PMID: 15668445 BACKGROUND

• Hobson-Webb LD, Proia AD, Thurberg BL, Banugaria S, Prater SN, Kishnani PS. Autopsy findings in late-onset Pompe disease: a case report and systematic review of the literature. Mol Genet Metab. 2012 Aug;106(4):462-9. doi: 10.1016/j.ymgme.2012.05.007. Epub 2012 May 18.

  PMID: 22664150 BACKGROUND

• Matsuoka Y, Hirayama M, Senda Y, Matsui T. [Two autopsy cases of adult-type acid maltase deficiency with vacuolation of cerebral arterial walls]. Rinsho Shinkeigaku. 1985 Jan;25(1):39-45. No abstract available. Japanese.

  PMID: 3922655 BACKGROUND

• Bijvoet AG, Van Hirtum H, Vermey M, Van Leenen D, Van Der Ploeg AT, Mooi WJ, Reuser AJ. Pathological features of glycogen storage disease type II highlighted in the knockout mouse model. J Pathol. 1999 Nov;189(3):416-24. doi: 10.1002/(SICI)1096-9896(199911)189:33.0.CO;2-6.

  PMID: 10547605 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Retained biospecimens include dried blood spot samples and blood samples for measurement of acid alpha-glucosidase (GAA) activity and GAA gene sequencing in participants with reduced GAA activity. Vascular tissue samples obtained during clinically indicated vascular interventions may also be retained for morphological analysis of glycogen deposition

MeSH Terms

Conditions

Glycogen Storage Disease Type II

Condition Hierarchy (Ancestors)

Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Glycogen Storage Disease; Carbohydrate Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 29, 2026
• First Posted: July 6, 2026
• Study Start: May 1, 2020
• Primary Completion: April 16, 2025
• Study Completion: April 16, 2025
• Last Updated: July 6, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)