A cross-sectional single-centre study on the spectrum of Pompe disease, German patients: molecular analysis of the GAA gene, manifestation and genotype-phenotype correlations

Andreas Herzog,Arnold J J Reuser,Seyfullah Gökce,Christoph Kampmann,Christina Lampe,Heiko Runz,Michael Beck,Ralf Hartung,Nesrin Karabul,Pia Hermanns,Joachim Pohlenz,Eugen Mengel

doi:10.1186/1750-1172-7-35

Abstract

BackgroundPompe disease (Glycogen storage disease type II, GSD II, acid alpha-glucosidase deficiency, acid maltase deficiency, OMIM # 232300) is an autosomal-recessive lysosomal storage disorder due to a deficiency of acid alpha-glucosidase (GAA, acid maltase, EC 3.2.1.20, Swiss-Prot P10253). Clinical manifestations are dominated by progressive weakness of skeletal muscle throughout the clinical spectrum. In addition, the classic infantile form is characterised by hypertrophic cardiomyopathy.MethodsIn a cross-sectional single-centre study we clinically assessed 3 patients with classic infantile Pompe disease and 39 patients with non-classic presentations, measured their acid alpha-glucosidase activities and analysed their GAA genes.ResultsClassic infantile patients had nearly absent residual enzyme activities and a typical clinical course with hypertrophic cardiomyopathy until the beginning of therapy. The disease manifestations in non-classic patients were heterogeneous. There was a broad variability in the decline of locomotive and respiratory function. The age of onset ranged from birth to late adulthood and correlated with enzyme activities. Molecular analysis revealed as many as 33 different mutations, 14 of which are novel. All classic infantile patients had two severe mutations. The most common mutation in the non-classic group was c.-32-13 T > G. It was associated with a milder course in this subgroup.ConclusionsDisease manifestation strongly correlates with the nature of the GAA mutations, while the variable progression in non-classic Pompe disease is likely to be explained by yet unknown modifying factors. This study provides the first comprehensive dataset on the clinical course and the mutational spectrum of Pompe disease in Germany.

Highlights

Pompe disease (Glycogen storage disease type II, GSD II, acid alpha-glucosidase deficiency, acid maltase deficiency, OMIM # 232300) is an autosomal-recessive lysosomal storage disorder caused by a deficiency of acid alpha-glucosidase (GAA, acid maltase, EC 3.2.1.20, SwissProt P10253) [1]
This early intervention resulted in normalisation of the left ventricular wall thickness and a near normal development of the creatine kinase (CK) [U/l] lactate dehydrogenase (LDH) [U/l] alanine aminotransferase (ALAT) [U/l] aspartate aminotransferase (ASAT) [U/l]
Additional sensitive hints can be given by serum values of CK, LDH, ALAT and ASAT that were clearly elevated in most patients

Summary

Introduction

Pompe disease (Glycogen storage disease type II, GSD II, acid alpha-glucosidase deficiency, acid maltase deficiency, OMIM # 232300) is an autosomal-recessive lysosomal storage disorder due to a deficiency of acid alpha-glucosidase (GAA, acid maltase, EC 3.2.1.20, Swiss-Prot P10253). Clinical manifestations are dominated by progressive weakness of skeletal muscle throughout the clinical spectrum. Pompe disease (Glycogen storage disease type II, GSD II, acid alpha-glucosidase deficiency, acid maltase deficiency, OMIM # 232300) is an autosomal-recessive lysosomal storage disorder caused by a deficiency of acid alpha-glucosidase (GAA, acid maltase, EC 3.2.1.20, SwissProt P10253) [1]. Accumulation of glycogen in various tissues leads to a broad and continuous spectrum of clinical phenotypes that can be categorised according to clinical features into classic infantile and non-classic forms. Most of classic infantile patients die within the first year of life [2,3]

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