Phenotypical variation within 22 families with Pompe disease

Orphanet Journal of Rare Diseases

Esther Brusse²  Ans T van der Ploeg¹  Pieter A van Doorn²  Arnold J J Reuser³  Nadine A M E van der Beek²  Juna M de Vries²  Michelle E Kruijshaar²  Carin M van Gelder¹  Stephan C A Wens² 

[1] Department of Pediatrics, Division of Metabolic Diseases and Genetics, Erasmus MC-Sophia, Rotterdam, The Netherlands;Centre for Lysosomal and Metabolic Diseases, Erasmus MC, ‘s-Gravendijkwal 230, 3015 CE Rotterdam, the Netherlands;Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands

关键词: Siblings;    Families;    Phenotype;    Acid α-glucosidase;    Lysosomal storage disorder;    Glycogen storage disease type II;    Pompe disease;   

Others  :  863411
DOI  :  10.1186/1750-1172-8-182

 received in 2013-07-30, accepted in 2013-11-16,  发布年份 2013

【 摘 要 】

Background

Pompe disease has a broad clinical spectrum, in which the phenotype is partially explained by the genotype. The aim of this study was to describe phenotypical variation among siblings with non-classic Pompe disease. We hypothesized that siblings and families with the same genotype share more similar phenotypes than the total population of non-classic Pompe patients, and that this might reveal genotype-phenotype correlations.

Methods

We identified all Dutch families in which two or three siblings were diagnosed with Pompe disease and described genotype, acid α-glucosidase activity, age at symptom onset, presenting symptoms, specific clinical features, mobility and ventilator dependency.

Results

We identified 22 families comprising two or three siblings. All carried the most common mutation c.-32-13 T > G in combination with another pathogenic mutation. The median age at symptom onset was 33 years (range 1–62 years). Within sibships symptom onset was either in childhood or in adulthood. The median variation in symptom onset between siblings was nine years (range 0–31 years). Presenting symptoms were similar across siblings in 14 out of 22 families. Limb girdle weakness was most frequently reported. In some families ptosis or bulbar weakness were present in all siblings. A large variation in disease severity (based on wheelchair/ventilator dependency) was observed in 11 families. This variation did not always result from a difference in duration of the disease since a third of the less affected siblings had a longer course of the disease. Enzyme activity could not explain this variation either. In most families male patients were more severely affected. Finally, symptom onset varied substantially in twelve families despite the same GAA genotype.

Conclusion

In most families with non-classic Pompe disease siblings share a similar phenotype regarding symptom onset, presenting symptoms and specific clinical features. However, in some families the course and severity of disease varied substantially. This phenotypical variation was also observed in families with identical GAA genotypes. The commonalities and differences indicate that besides genotype, other factors such as epigenetic and environmental effects influence the clinical presentation and disease course.

【 授权许可】

   
2013 Wens et al.; licensee BioMed Central Ltd.

【 图 表 】

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