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J Cell Physiol. 2018 Aug;233(8):5829-5837. doi: 10.1002/jcp.26365. Epub 2018 Feb 22.

Vacuolated PAS-positive lymphocytes as an hallmark of Pompe disease and other myopathies related to impaired autophagy.

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2nd Division of Neurology, Department of Medicine, Surgery, Neurology, Metabolic and Aging Science, Reference Center for Neurological and Neuromuscular Rare Disease & Interuniversity Center for Research in Neurosciences, University of Campania "Luigi Vanvitelli", Naples, Italy.
Neurorehabilitation Unit and Research Lab. for Disorder of Consciousness, Maugeri ICS, Telese Terme, Italy.
Division of Clinical Biochemistry, Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy.
Molecular Genetics and Genomics Laboratory, Institute of Genetics and Biophysics, "Adriano Buzzati Traverso", Italian National Research Council (CNR), Naples, Italy.
IRCCS INM Neuromed, Pozzilli, Italy.
Department of Experimental and Clinical Biomedical Sciences, University of Florence; Head, Newborn Screening, Clinical Chemistry and Pharmacology Lab, Meyer Offspring's Hospital, Florence, Italy.
Department of Biology, Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, Pennsylvania.
Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy.

Erratum in


Autosomal recessive Pompe disease is a lysosomal disorder caused by mutations of the acid-α-glucosidase (GAA) gene. Deficiency of GAA enzyme leads to glycogen accumulation and autophagy impairment in cardiac and skeletal muscles, but also in lymphocytes. Since an effective therapy is available, a rapid, sensitive, and specific test is crucial to early identify affected subjects. Number of lymphocytes containing PAS-positive vacuoles was evaluated on blood films from 72 consecutive adult patients with hyperckemia and/or muscle weakness, 13 genetically confirmed late-onset-Pompe-disease (LOPD) and 13 of their offspring. GAA activity, measured on dried blood spot (DBS) in all patients inversely correlated with number of PAS-positive lymphocytes. More than 4 PAS-positive lymphocytes were found in 11 out of the 72 patients (6 new diagnosis of LOPD, 3 different glycogen storage myopathies, 1 glucose-6-phosphate dehydrogenase deficiency, 1 caveolinopathy), in all 13 LOPD patients and in the 13 LOPD offspring. These latter resulted to have all a single GAA mutation but low GAA levels. Immunostaining with the autophagy markers LC3 and p62 confirmed the autophagic nature of lymphocytes vacuoles. ROC curve assessment of PAS-positive lymphocytes disclosed 100% of sensitivity and 94% of specificity in recognizing both compound heterozygous and heterozygous GAA carriers. The other myopathies with more than 4 PAS-positive lymphocytes appeared to be all related to impaired autophagy, which seems to be responsible of PAS-positive vacuolated lymphocytes formation. Quantification of PAS-positive lymphocytes in blood films is useful to identify autophagic vacuolar myopathies and should be routinely used as first level test for Pompe disease.


GSD II diagnostic algorithm; PAS-positive lymphocytic granules; Pompe disease; glycogen storage myopathies; screening method for glycogenosis


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