Pompe disease in Austria: clinical, genetic and epidemiological aspects

W N Löscher,C Eggers,R E Bittner,T M Stulnig,M Huemer,S Grinzinger,J V Wanschitz,S Quasthoff,M Reichhardt,U Lex,M Freilinger,P Simschitz,S Iglseder,D Möslinger,M Brunner-Krainz,W M Schmidt,F Lagler,H Moser

doi:10.1007/s00415-017-8686-6

Abstract

In this study, we performed a survey of infantile and late-onset Pompe disease (IOPD and LOPD) in Austria. Paediatric and neuromuscular centres were contacted to provide a set of anonymized clinical and genetic data of patients with IOPD and LOPD. The number of patients receiving enzyme replacement therapy (ERT) was obtained from the pharmaceutical company providing alglucosidase alfa. We found 25 patients in 24 families, 4 IOPD and 21 LOPD with a resulting prevalence of 1:350,914. The most frequent clinical manifestation in LOPD was a lower limb-girdle phenotype combined with axial weakness. Three patients were clinically pauci- or asymptomatic and were diagnosed because of persistent hyperCKemia. Diagnostic delay in LOPD was 7.4 ± 9.7 years. The most common mutation was c.-32-13T > G. All IOPD and 17 symptomatic LOPD patients are receiving ERT. Standardized follow-up was only available in six LOPD patients for the 6-min walk test (6minWT) and in ten for the forced vital capacity (FVC). Mean FVC did not decline (before ERT; 63.6 ± 39.7%; last evaluation during ERT: 61.9 ± 26.9%; P = 0.5) while there was a trend to decline in the mean distance covered by the 6minWT (before ERT: 373.5 ± 117.9 m; last evaluation during ERT: 308.5 ± 120.8 m; P = 0.077). The study shows a lower prevalence of Pompe disease in Austria than in other European countries and corroborates a limb-girdle phenotype with axial weakness as the most common clinical presentation, although asymptomatic hyperCKemia may be the first indication of LOPD.

Highlights

IntroductionKnown as glycogenosis type 2 or acid maltase deficiency, is an autosomal recessive disease caused by > 450 mutations in the GAA gene (http://cluster15.erasmusmc.nl/klgn/pompe/mutations.html) which lead to deficiency of the lysosomal enzyme acid alphaglucosidase [1]
Pompe disease, known as glycogenosis type 2 or acid maltase deficiency, is an autosomal recessive disease caused by > 450 mutations in the GAA gene which lead to deficiency of the lysosomal enzyme acid alphaglucosidase [1]
Genetic and epidemiologic data on this rare disease and to provide results on the effects of enzyme replacement therapy (ERT), we report the Austrian cohort of IOPD and LOPD patients

Summary

Introduction

Known as glycogenosis type 2 or acid maltase deficiency, is an autosomal recessive disease caused by > 450 mutations in the GAA gene (http://cluster15.erasmusmc.nl/klgn/pompe/mutations.html) which lead to deficiency of the lysosomal enzyme acid alphaglucosidase [1]. Depending on residual enzyme activity symptoms may develop during the first months of life (infantile-onset Pompe disease, IOPD) or during childhood, adolescence or adulthood (late-onset Pompe disease, LOPD) [2]. Untreated IOPD causes rapidly progressive muscle weakness and cardiomyopathy which usually is fatal within 1–2 years [3]. LOPD generally takes a milder course with slowly progressive muscle weakness without cardiomyopathy. It is assumed that the prevalence is higher as several studies in patients with unexplained myopathies detected new cases with undiagnosed LOPD [5, 6]. Since enzyme replacement therapy (ERT) has become the standard treatment for Pompe disease [7], increased efforts have been undertaken to further delineate the phenotype of Pompe disease to allow early diagnosis and treatment

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Conclusion