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Neuropediatrics 2022; 53(01): 039-045
DOI: 10.1055/s-0041-1735250
Original Article

Clinical and Genetic Aspects of Juvenile Onset Pompe Disease

Johanna Holzwarth
1   Department of Child Neurology, Justus-Liebig University Gießen, Germany
,
Nadja Minopoli
1   Department of Child Neurology, Justus-Liebig University Gießen, Germany
,
Charlotte Pfrimmer
1   Department of Child Neurology, Justus-Liebig University Gießen, Germany
,
Martin Smitka
2   Children's hospital, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
,
Sabine Borrel
3   Department of Neuropediatrics and Muscle Disorders, Medical Center-University of Freiburg, Freiburg, Germany
,
Janbernd Kirschner
3   Department of Neuropediatrics and Muscle Disorders, Medical Center-University of Freiburg, Freiburg, Germany
,
Nicole Muschol
4   Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
,
Hans Hartmann
5   Hannover Medical School, Clinic for Pediatric Kidney, Liver and Metabolic Diseases, Hannover, Germany
,
Julia B. Hennermann
6   Villa Metabolica, Department of Pediatric and Adolescent Medicine, University Medical Center Mainz, Mainz, Germany
,
Bernd A. Neubauer
1   Department of Child Neurology, Justus-Liebig University Gießen, Germany
,
Elke Hobbiebrunken
7   Department of Pediatrics and Adolescent Medicine, Division of Pediatric Neurology, University Medical Center Göttingen, Georg August University, Göttingen, Germany
,
Ralf A. Husain 
8   Centre for Inborn Metabolic Disorders, Department of Neuropediatrics, Jena University Hospital, Jena, Germany
,
Andreas Hahn
1   Department of Child Neurology, Justus-Liebig University Gießen, Germany
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Abstract

Little 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.

Keywords

Pompe disease - glucosidase - phenotype - genotype


Publication History

Received: 30 December 2020

Accepted: 27 July 2021

Article published online:
01 December 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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