The phenotype of juvenile-onset Pompe disease is broad and the differential is not only restricted to neuromuscular disorders, according to a new study published in the journal Neuropediatrics.

Genotypic analysis can be useful to identify patients with early juvenile-onset Pompe disease from patients with infantile-onset disease, but the overall genotype-phenotype correlation was poor, the authors said.

The symptoms and genetics of juvenile-onset Pompe disease are not clear. A team of researchers from the Justus-Liebig University in Giessen, Germany aimed to analyze how children with juvenile-onset Pompe disease are diagnosed, what their clinical complications are, and what their genotype and phenotype relationships are.

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To do so, the team retrospectively analyzed data from 34 patients who were diagnosed with Pompe disease aged between 1 and 18 years. The median age of the patients when they were diagnosed was 3.9 years. 

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Of the 34 patients, 8 (23.5%) had their first symptoms in their first year. More than 35% of the patients developed the first symptoms of the disease when they were aged between 1 and 7 years. Six patients (18%) developed symptoms after age 7, and a total of 8 patients did not have any clinical symptoms when they were diagnosed with the disease.

Indications for diagnostics were as follows: a positive family history, hyperCKemia, motor developmental delays, and muscle weakness and/or pain. Clinical signs of the disease included failure to thrive, recurrent diarrhea, and suspected hepatopathy. 

Of the 8 patients who had symptoms in their first year, 3 needed ventilation, had generalized muscle weakness, and hypertrophic cardiomyopathy. This meant that their diseases clinically overlapped with infantile-onset Pompe disease.

When the researchers analyzed the patients genetically, they identified 32 different genetic mutations. The majority of patients (79.5%) carried the milder c.32–13T > G mutation. This mutation is associated with a broad range of phenotypes. 

The researchers said that their study shows that genotyping helps distinguish juvenile-onset Pompe disease from infantile-onset disease.

Pompe disease can be classified as infantile-onset and late-onset. Late-onset Pompe disease can further be divided into adult-onset Pompe disease and juvenile-onset Pompe disease. Juvenile-onset Pompe disease can manifest at any stage of development including infancy, childhood, and adolescence.


Holzwarth J, Minopoli N, Pfrimmer C, et al. Clinical and genetic aspects of juvenile onset Pompe disease. Neuropediatrics. Published online December 1, 2021. doi:10.1055/s-0041-1735250