Clinical and Genetic Aspects of Juvenile Onset Pompe Disease

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Johanna Holzwarth - , Justus Liebig University Giessen (Author)
  • Nadja Minopoli - , Justus Liebig University Giessen (Author)
  • Charlotte Pfrimmer - , Justus Liebig University Giessen (Author)
  • Martin Smitka - , Department of Paediatrics, Division of Neuropediatrics (Author)
  • Sabine Borrel - , University of Freiburg (Author)
  • Janbernd Kirschner - , University of Freiburg (Author)
  • Nicole Muschol - , Medical University Sofia (Author)
  • Hans Hartmann - , Hannover Medical School (MHH) (Author)
  • Julia B. Hennermann - , Johannes Gutenberg University Mainz (Author)
  • Bernd A. Neubauer - , Justus Liebig University Giessen (Author)
  • Elke Hobbiebrunken - , University of Göttingen (Author)
  • Ralf A. Husain - , Friedrich Schiller University Jena (Author)
  • Andreas Hahn - , Justus Liebig University Giessen (Author)

Abstract

AbstractLittle is known about clinical symptomatology and genetics of juvenile onset Pompe disease (JOPD). The aims of this study were to analyze how these children are diagnosed, what clinical problems they have, and how phenotype is related to genotype. To accomplish this, we analyzed retrospectively data of 34 patients diagnosed after their first and before completion of their 18th birthday. Median age at diagnosis was 3.9 (range 1.1–17) years. Eight patients (23.5%) developed initial symptoms in the first year, 12 (35%) between 1 and 7 years, and 6 (18%) thereafter. Eight (23.5%) had no clinical symptoms at the time of diagnosis. Indications for diagnostics were a positive family history in three (9%), hyperCKemia in eight (23.5%), motor developmental delay in three (9%), and muscle weakness and/or pain in 17 (50%). Rare clinical signs were failure to thrive, recurrent diarrhea, and suspected hepatopathy with glycogen storage. Thirty-two different mutations were identified. Twenty-seven patients (79.5%) carried the milder c.32–13T > G mutation, known to be associated with a broad range of phenotypes. Three out of eight patients manifesting within the first year of life showed generalized muscle weakness, hypertrophic cardiomyopathy, and had to be ventilated during the course of disease, thereby demonstrating clinical overlap with infantile onset Pompe disease.These findings demonstrate that the phenotype of JOPD is broad and that the differential is not only restricted to neuromuscular disorders. Genotypic analysis was useful to delineate subjects with early onset JOPD from those with IOPD, but overall genotype–phenotype correlation was poor.

Details

Original languageEnglish
Pages (from-to)39-45
Number of pages7
JournalNeuropediatrics
Volume53
Issue number1
Publication statusPublished - 1 Feb 2022
Peer-reviewedYes

External IDs

PubMed 34852371

Keywords

Sustainable Development Goals

Keywords

  • genotype, glucosidase, phenotype, Pompe disease