Researchers identified a new, more sensitive screening test to recognize Pompe disease, a metabolic disorder affecting cellular processing of glycogen in numerous tissues of the body. The test detects the presence of more than four lymphocytes containing glycogen in blood films of subjects with suspicious neuromuscular disease, and has demonstrated 100% sensitivity and 94% specificity identifying patients with Pompe disease. Moreover, positivity of vacuolated lymphocytes to the Periodic-Acid Schiff staining (PAS) seems to be an hallmark of autophagic myopathies. This new method of detection will allow clinicians to differentiate Pompe disease and autophagic myopathies from other neuromuscular disorders more accurately.

The study was published online in December 2017, in the Journal of Cellular Physiology.

Pompe disease, also known as Glycogen storage disease type II, is a metabolic disorder caused by an accumulation of glycogen in the lysosomes due to a deficiency of alpha-glucosidase, a lysosomal enzyme acid. The build-up of glycogen affects various body tissues, particularly heart, skeletal and respiratory muscles, as well as lymphocytes in peripheral blood. The classic infantile form of Pompe disease, presenting with marked generalized muscle weakness and severe hypertrophic cardiomyopathy, rapidly progresses to a fatal outcome. The late-onset form is characterized by slowly progressive myopathy involving proximal, limb-girdle, paraspinal, and respiratory muscles without cardiac involvement. Vacuolar myopathy typical of Pompe disease is the most frequent myopathy due to an impairment of autophagy, the main natural mechanism necessary to degrade and recycle cellular components.

Enzyme replacement therapy for Pompe disease became available in 2006 and resulted in dramatic reduction of mortality and morbidity for Pompe patients. The discovery and commercialization of this therapy figure prominently in the plot of the 2010 film “Extraordinary Measures,” starring Harrison Ford and Brendan Fraser. Since an early start of therapy is associated with better clinical outcomes, early diagnosis is essential in order to achieve the maximum benefit.

The research was conducted by a team of scientists lead by Dr. Simone Sampaolo and Mariarosa AB Melone, Department of Medicine, Surgery, Neurology, Metabolic and Aging Science, Reference Center for Neurological and Neuromuscular Rare Disease, University of Campania “Luigi Vanvitelli”, Naples, in collaboration with Dr. Antonio Giordano, Director of the Sbarro Institute for Cancer Research and Department of Biology at Temple University, Philadelphia.

Pompe disease is an underdiagnosed disorder, and considering that therapy is now available, early diagnosis is crucial to obtain the best prognosis. This research proposes a reliable, cheap, simple, first-level screening method to support the diagnosis of autophagic vacuolar myopathy as Pompe disease. The test is minimally invasive and could be used as a screening test in high-risk populations, such as pregnant women and people with a family history of neuromuscular disorders.