Format

Send to

Choose Destination
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.

Author information

1
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.
2
Neurorehabilitation Unit and Research Lab. for Disorder of Consciousness, Maugeri ICS, Telese Terme, Italy.
3
Division of Clinical Biochemistry, Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy.
4
Molecular Genetics and Genomics Laboratory, Institute of Genetics and Biophysics, "Adriano Buzzati Traverso", Italian National Research Council (CNR), Naples, Italy.
5
IRCCS INM Neuromed, Pozzilli, Italy.
6
Department of Experimental and Clinical Biomedical Sciences, University of Florence; Head, Newborn Screening, Clinical Chemistry and Pharmacology Lab, Meyer Offspring's Hospital, Florence, Italy.
7
Department of Biology, Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, Pennsylvania.
8
Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy.

Erratum in

Abstract

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.

KEYWORDS:

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

PMID:
29215735
DOI:
10.1002/jcp.26365

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center