Homozygosity for the common GAA gene splice site mutation c.-32-13T>G in Pompe disease is associated with the classical adult phenotypical spectrum

Olimpia Musumeci, Andrea Thieme, Kristl G. Claeys, Stephan Wenninger, Rudolf A. Kley, Marius Kuhn, Zoltan Lukacs, Marcus Deschauer, Michele Gaeta, Antonio Toscano, Dieter Gläser, Benedikt Schoser

Research output: Contribution to journalArticlepeer-review

Abstract

Homozygosity for the common Caucasian splice site mutation c.-32-13T>G in intron 1 of the GAA gene is rather rare in Pompe patients. We report on the clinical, biochemical, morphological, muscle imaging, and genetic findings of six adult Pompe patients from five unrelated families with the c.-32-13T>G GAA gene mutation in homozygous state. All patients had decreased GAA activity and elevated creatine kinase levels. Five patients, aged between 43 and 61 years (median 53 years), initially presented with myalgia, hyperCKaemia, and/or exercise induced fatigue at an age of onset (12-55 years). All but one had proximal lower limb weakness combined with axial weakness and moderate respiratory insufficiency; the sixth patient presented with hyperCKaemia only. Muscle biopsies showed PAS-positive vacuolar myopathy with lysosomal changes and reduced GAA activity. Muscle MRI of lower limb muscles revealed a moderate adipose substitution of the gluteal muscles, biceps femoris and slight fatty infiltration of all thigh muscles. One MRI of the respiratory muscles revealed a diaphragmatic atrophy with unilateral diaphragm elevation. So, the common Caucasian, so called mild, splice site mutation c.-32-13T>G in intron 1 of the GAA gene in a homozygote status reflects the full adult Pompe disease phenotype severity spectrum.

Original languageEnglish
Pages (from-to)719-724
Number of pages6
JournalNeuromuscular Disorders
Volume25
Issue number9
DOIs
Publication statusPublished - Sep 1 2015

Keywords

  • GAA mutation
  • GAA-MLPA
  • Glycogen storage disease type 2
  • Homozygosity
  • Pompe disease

ASJC Scopus subject areas

  • Clinical Neurology
  • Pediatrics, Perinatology, and Child Health
  • Genetics(clinical)
  • Neurology

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