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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 J Rare Dis 2012; 7:35OJ

Abstract

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.-32-13T>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.

Authors+Show Affiliations

Center for Pediatric and Adolescent Medicine, University Medical Center, Mainz, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22676651

Citation

Herzog, Andreas, et al. "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, vol. 7, 2012, p. 35.
Herzog A, Hartung R, Reuser AJ, et al. 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 J Rare Dis. 2012;7:35.
Herzog, A., Hartung, R., Reuser, A. J., Hermanns, P., Runz, H., Karabul, N., ... Mengel, E. (2012). 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, 7, p. 35. doi:10.1186/1750-1172-7-35.
Herzog A, et al. 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 J Rare Dis. 2012 Jun 7;7:35. PubMed PMID: 22676651.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Herzog,Andreas, AU - Hartung,Ralf, AU - Reuser,Arnold J J, AU - Hermanns,Pia, AU - Runz,Heiko, AU - Karabul,Nesrin, AU - Gökce,Seyfullah, AU - Pohlenz,Joachim, AU - Kampmann,Christoph, AU - Lampe,Christina, AU - Beck,Michael, AU - Mengel,Eugen, Y1 - 2012/06/07/ PY - 2012/01/31/received PY - 2012/06/07/accepted PY - 2012/6/9/entrez PY - 2012/6/9/pubmed PY - 2013/2/15/medline SP - 35 EP - 35 JF - Orphanet journal of rare diseases JO - Orphanet J Rare Dis VL - 7 N2 - 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.-32-13T>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. SN - 1750-1172 UR - https://www.unboundmedicine.com/medline/citation/22676651/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_ L2 - https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-7-35 DB - PRIME DP - Unbound Medicine ER -