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

P Vanherpe,K G Claeys,J Baets,P Van Damme,C Bleyenheuft,B Buyse,P Van Den Bergh,P Demaerel,A D’Hondt,S Delstanche,G Remiche,K Verhoeven,S Fieuws,C E Depuydt,M Toussaint,J De Bleecker

doi:10.1186/s13023-020-01353-4

Abstract

BackgroundLate-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).MethodsWe 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.ResultsIn 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).ConclusionsAwareness 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.

Highlights

Pompe disease, known as glycogen storage disease type 2 (GSD2) or acid maltase deficiency, is an autosomal recessive disorder caused by a deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA), resulting in the accumulation of glycogen in muscle cells
We studied the following functional data in the period between 2010 and 2017: forced vital capacity (FVC) in sitting and supine position, 6-min walk distance (6MWD), 10-m walk test (10MWT), Medical Research Council (MRC) sum score, and the ActivLim questionnaire [11,12,13]
For the 6MWD, MRC sum score, FVC sitting and FVC supine, we measured a significant decrease over time in Late-onset Pompe disease (LOPD) patients, even though they were treated with enzyme replacement therapy (ERT)

Summary

Introduction

Known as glycogen storage disease type 2 (GSD2) or acid maltase deficiency, is an autosomal recessive disorder caused by a deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA), resulting in the accumulation of glycogen in muscle cells. This usually leads to progressive limb-girdle muscle weakness and respiratory insufficiency, but heart, liver and the nervous system can be affected [1,2,3,4,5]. 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

Results

Discussion

Conclusion