Late-onset Pompe disease (LOPD) in Belgium: clinical characteristics and outcome measures.

6MWD; ActivLim; Belgian cohort; GSD2; Glycogen storage disease type 2; Respiratory; alpha-Glucosidases; Belgium/epidemiology; Delayed Diagnosis; Enzyme Replacement Therapy; Humans; Middle Aged; Outcome Assessment, Health Care; alpha-Glucosidases/therapeutic use; Glycogen Storage Disease Type II/drug therapy; Glycogen Storage Disease Type II/epidemiology; Glycogen Storage Disease Type II/genetics; Belgium; Glycogen Storage Disease Type II; Genetics (clinical); Pharmacology (medical)

Abstract :

[en] [en] BACKGROUND: Late-onset Pompe disease (LOPD) is a rare, hereditary, progressive disorder that is usually characterized by limb-girdle muscle weakness and/or respiratory insufficiency. LOPD is caused by mutations in the acid alpha-glucosidase (GAA) gene and treated with enzyme replacement therapy (ERT). METHODS: We studied the clinical, brain imaging, and genetic features of the Belgian cohort of late-onset Pompe disease patients (N = 52), and explored the sensitivity of different outcome measures, during a longitudinal period of 7 years (2010-2017), including the activity limitations ActivLim score, 6 min walking distance (6MWD), 10 m walk test (10MWT), MRC sum score, and forced vital capacity (FVC) sitting/supine. RESULTS: In Belgium, we calculated an LOPD prevalence of 3.9 per million. Mean age at onset of 52 LOPD patients was 28.9 years (SD: 15.8 y), ranging from 7 months to 68 years. Seventy-five percent (N = 39) of the patients initially presented with limb-girdle weakness, whereas in 13% (N = 7) respiratory symptoms were the only initial symptom. Non-invasive ventilation (NIV) was started in 37% (N = 19), at a mean age of 49.5 years (SD: 11.9 y), with a mean duration of 15 years (SD: 10.2 y) after symptom onset. Brain imaging revealed abnormalities in 25% (N = 8) of the patients, with the presence of small cerebral aneurysm(s) in two patients and a vertebrobasilar dolichoectasia in another two. Mean diagnostic delay was 12.9 years. All patients were compound heterozygotes with the most prevalent mutation being c.-32-13 T > G in 96%. We identified two novel mutations in GAA: c.1610_1611delA and c.186dup11. For the 6MWD, MRC sum score, FVC sitting and FVC supine, we measured a significant decrease over time (p = 0.0002, p = 0.0001, p = 0.0077, p = 0.0151), which was not revealed with the ActivLim score and 10MWT (p > 0.05). CONCLUSIONS: Awareness on LOPD should even be further increased because of the long diagnostic delay. The 6MWD, but not the ActivLim score, is a sensitive outcome measure to follow up LOPD patients.

Disciplines :

Neurology

Author, co-author :

Vanherpe, P; Department of Neurology, Neuromuscular Reference Centre, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium

Fieuws, S; KU Leuven - University of Leuven, Interuniversity Institute for Biostatistics and Statistical Bioinformatics, Leuven, Belgium

D'Hondt, A; Department of Neurology, Neuromuscular Reference Centre, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium

Bleyenheuft, C; Sciensano, Brussels, Belgium

Demaerel, P; Department of Radiology, University Hospitals Leuven, Leuven, Belgium

De Bleecker, J; Department of Neurology, Neuromuscular Reference Centre, University Hospital Gent, Gent, Belgium

Van den Bergh, P; Department of Neurology, Neuromuscular Reference Centre, University Hospital Saint-Luc, Brussels, Belgium

Baets, J; Department of Neurology, Neuromuscular Reference Centre, University Hospital Antwerpen, Antwerpen, Belgium

Remiche, G; Department of Neurology, Neuromuscular Reference Centre, University Hospital Erasme, Université Libre de Bruxelles, Brussels, Belgium

Verhoeven, K; Department of Neurology, AZ Sint-Jan Brugge, Brugge, Belgium

More authors (6 more)

Language :

English

Title :

Late-onset Pompe disease (LOPD) in Belgium: clinical characteristics and outcome measures.

Publication date :

05 April 2020

Journal title :

Orphanet Journal of Rare Diseases

eISSN :

1750-1172

Publisher :

BioMed Central Ltd., England

Volume :

Issue :

Pages :

Peer reviewed :

Peer Reviewed verified by ORBi

Additional URL :

http://link.springer.com/content/pdf/10.1186/s13023-020-01353-4.pdf

Available on ORBi :

since 09 July 2025

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