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Neuromuscul Disord. 2014 Dec;24(12):1079-86. doi: 10.1016/j.nmd.2014.08.002. Epub 2014 Aug 21.

PYGM expression analysis in white blood cells: a complementary tool for diagnosing McArdle disease?

Author information

1
Mitochondrial Pathology and Neuromuscular Disorders laboratory, Vall d'Hebron Research Institute, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Spain.
2
Universidad Europea and Instituto de Investigación 'i+12', Madrid, Spain.
3
Universidad Pablo de Olavide, Seville, Spain.
4
Facultad de Ciencias de la Salud y del Deporte, Universidad de Zaragoza, Huesca, Spain.
5
Mitochondrial Pathology and Neuromuscular Disorders laboratory, Vall d'Hebron Research Institute, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Spain. Electronic address: toniandreu.bcn@gmail.com.
6
Mitochondrial Pathology and Neuromuscular Disorders laboratory, Vall d'Hebron Research Institute, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Spain. Electronic address: tomas.pinos@vhir.org.

Abstract

McArdle disease is caused by an inherited deficiency of the enzyme myophosphorylase, resulting in exercise intolerance from childhood and acute crises of early fatigue and contractures. In severe cases, these manifestations can be accompanied by rhabdomyolysis, myoglobinuria, and fatal renal failure. Diagnosis of McArdle disease is based on clinical diagnostic tests, together with an absence of myophosphorylase activity in skeletal muscle biopsies and genetic analysis of the myophosphorylase-encoding gene, PYGM. The recently reported association between myophosphorylase and Rac1 GTPase in a T lymphocyte cell line prompted us to study myophosphorylase expression in white blood cells (WBCs) from 20 healthy donors and 30 McArdle patients by flow cytometry using a fluorescent-labeled PYGM antibody. We found that T lymphocytes expressed myophosphorylase in healthy donors, but expression was significantly lower in McArdle patients (p<0.001). PYGM mRNA levels were also lower in white blood cells from McArdle patients. Nevertheless, in 13% of patients (who were either heterozygotes or homozygotes for the most common PYGM pathogenic mutation among Caucasians (p.R50X)), the percentage of myophosphorylase-positive white blood cells was not different compared with the control group. Our findings suggest that analysis of myophosphorylase expression in white blood cells might be a useful, less-invasive, complementary test for diagnosing McArdle disease.

KEYWORDS:

Diagnosis; Flow cytometry; McArdle disease; Myophosphorylase; White blood cells

PMID:
25240406
DOI:
10.1016/j.nmd.2014.08.002
[Indexed for MEDLINE]

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