Morphological changes in Late Onset Acid Maltase Deficient Patients with splicing gene mutation

Corrado Angelini, G. Cenacchi, A. C. Nascimbeni, L. Fulizio

Research output: Contribution to journalArticlepeer-review


Clinical and morphological features have been studied in 11 late onset Acid Maltase Deficient (AMD) patients. All patients have been diagnosed on biochemical evidence of acid maltase deficiency on muscle biopsy. Molecular studies showed a heterozygous mutation (IVS1-13 T>G transversion resulting in aberrant splicing) in the GSDII gene, which is the most common mutation in late onset AMD patients. Morphological features in muscle biopsy showed a vacuolar myopathy and Golgi apparatus proliferation within fibres. The peripheral areas of autophagic vacuoles were positive for caveolin-3 and dystrophin, documenting an extensive membrane turnover. The ultrastructural study of muscle biopsy showed randomly distributed or isolated vesicles sometimes derived from the Golgi apparatus. In subsarcolemmal region, lipofucsin bodies and abnormal mitochondria with crystalline inclusions were observed. Primary and secondary lysosomes were typically filled with glycogen. These data suggest a predominant role of Golgi in vesicle proliferation and extensive intra-fibral membrane remodelling. The pathological changes observed are selective for muscle fibres (mostly in type 1) and for muscle groups (mainly proximal). An attractive hypothesis for the variability of clinical phenotype in adult and infantile onset AMD patients is that in the former, an aberrant transcript of smaller size may have originated from alternative splicing (exon 2 skipping). A residual enzyme activity is detectable in muscle, but the intracellular processing of the enzyme precursor from Golgi to the mature form in lysosomes might be blocked.

Original languageEnglish
Pages (from-to)90-96
Number of pages7
JournalActa Myologica
Issue numberDEC.
Publication statusPublished - Dec 2003


  • Acid maltase
  • Glycogen storage disease II
  • Golgi apparatus proliferation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology


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