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

Orphanet Journal of Rare Diseases

Eugen Mengel³  Michael Beck³  Christina Lampe³  Christoph Kampmann³  Joachim Pohlenz³  Seyfullah Gökce³  Nesrin Karabul³  Heiko Runz²  Pia Hermanns³  Arnold J J Reuser¹  Ralf Hartung³  Andreas Herzog³ 

[1] Department of Clinical Genetics, Erasmus MC University Medical Center, Dr Molewaterplein 50, 3015GE, Rotterdam, The Netherlands;Institute of Human Genetics, University of Heidelberg, Im Neuenheimer Feld 366, 69120, Heidelberg, Germany;Center for Pediatric and Adolescent Medicine, University Medical Center, Langenbeckstraße 1, 55131, Mainz, Germany

关键词: Enzyme replacement therapy;    Genotype phenotype correlations;    Lysosomal storage diseases;    GAA;    Pompe disease;    Glycogen storage disease type II;   

Others  :  864361
DOI  :  10.1186/1750-1172-7-35

 received in 2012-01-31, accepted in 2012-06-07,  发布年份 2012

【 摘 要 】

Background

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. In addition, the classic infantile form is characterised by hypertrophic cardiomyopathy.

Methods

In 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.

Results

Classic 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.

Conclusions

Disease 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.

【 授权许可】

   
2012 Herzog et al.; licensee BioMed Central Ltd.

【 图 表 】

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