Clinical and Genetic Aspects of Juvenile Onset Pompe Disease

Johanna Holzwarth; Nadja Minopoli; Charlotte Pfrimmer; Martin Smitka; Sabine Borrel; Janbernd Kirschner; Nicole Muschol; Hans Hartmann; Julia B. Hennermann; Bernd A. Neubauer; Elke Hobbiebrunken; Ralf A. Husain; Andreas Hahn

doi:10.1055/s-0041-1735250

Neuropediatrics, Inhaltsverzeichnis

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

¹Department of Child Neurology, Justus-Liebig University Gießen, Germany

,

Nadja Minopoli

¹Department of Child Neurology, Justus-Liebig University Gießen, Germany

,

Charlotte Pfrimmer

¹Department of Child Neurology, Justus-Liebig University Gießen, Germany

,

Martin Smitka

²Children's hospital, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

,

Sabine Borrel

³Department of Neuropediatrics and Muscle Disorders, Medical Center-University of Freiburg, Freiburg, Germany

,

Janbernd Kirschner

³Department of Neuropediatrics and Muscle Disorders, Medical Center-University of Freiburg, Freiburg, Germany

,

Nicole Muschol

⁴Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

,

Hans Hartmann

⁵Hannover Medical School, Clinic for Pediatric Kidney, Liver and Metabolic Diseases, Hannover, Germany

,

Julia B. Hennermann

⁶Villa Metabolica, Department of Pediatric and Adolescent Medicine, University Medical Center Mainz, Mainz, Germany

,

Bernd A. Neubauer

¹Department of Child Neurology, Justus-Liebig University Gießen, Germany

,

Elke Hobbiebrunken

⁷Department of Pediatrics and Adolescent Medicine, Division of Pediatric Neurology, University Medical Center Göttingen, Georg August University, Göttingen, Germany

,

Ralf A. Husain

⁸Centre for Inborn Metabolic Disorders, Department of Neuropediatrics, Jena University Hospital, Jena, Germany

,

Andreas Hahn

¹Department of Child Neurology, Justus-Liebig University Gießen, Germany

› Institutsangaben

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

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Referenzen

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