Disease severity and clinical outcome in phosphosglucomutase deficiency

Excerpt

Phosphoglucomutase 1 (PGM1) deficiency has been extensively studied since it was first described as a primary muscle disease more than 60 years ago (Thomson et al 1963). However, it is only recently that this inborn error has been redefined as both a muscle glycogenosis and a congenital disorder of glycosylation (Stojkovic et al 2009; Timal et al 2012; Tegtmeyer et al 2014). The PGM1 enzyme plays a central role in glucose homeostasis. It catalyzes the inter-conversion of glucose 1-phosphate and glucose 6-phosphate, which are important precursors for several metabolic pathways (Tegtmeyer et al 2014). Intriguingly, PGM1-CDG has two major phenotypes, one with predominantly muscle involvement and one with a multisystem involvement. The later phenotype includes congenital malformations (cleft palate, bifid uvula, cardiac valve malformations, anal atresia, vertebral anomalies), variable endocrine and hematological abnormalities, and cardiac and muscle disease (Scott et al 2014). So far, more than 20 different PGM1 mutations have been identified to be underlying to the complex phenotype and variable severity of PGM1-CDG (Morava 2014). …