P.124Is the expression of muscle glycogen phosphorylase tissue-specific? New perspectives on McArdle disease

Abstract

McArdle disease is a rare glycogen storage disorder with a reported incidence of ∼1:100.000 people. It is caused by recessive mutations in the gene encoding for muscle glycogen phosphorylase (MGP), which prevents the skeletal muscle from metabolizing stored glycogen. Until very recently, MGP expression was thought to be essentially restricted to the skeletal muscle tissue. Yet, we have shown that human T lymphocytes also express MGP, which in turn plays a key role to control the migration and proliferation capacity of these cells. This finding suggests that MGP could play an important role in regulating human immune function. In addition, our group has observed previously unreported co-morbidities in patients with McArdle disease including retinopathy, thyroid disease, neurocognitive symptoms and psychiatric disorders. Here we will report on the expression levels of the three glycogen phosphorylase isoforms (brain, liver and muscle [i.e., MGP]) in human immortalized thyroid follicular epithelial (Nthy-ori-3-1) and retinal pigmented epithelium cells (ARPE-19), and in human microglia and astrocytes. We will also present data showing that the absence of expression MGP in Nthy-ori-3-1 and ARPE-19 modifies its biological functions.