Congenital disorder of glycosylation – one size does not fit all: a parent’s perspective

This article is written by the parent of a child living with PMM2-congenital disorder of glycosylation (abbreviated to PMM2-CDG). It provides a parental perspective of the journey taken from diagnosis to present day and details the effect of off-label treatment with epalrestat. Plain Language Summary What is PMM2-CDG? PMM2-CDG is a rare multisystem disorder that involves a normal, but complex, chemical process known as glycosylation. Glycosylation is the process by which sugar chains (glycans) are created, altered and chemically attached to certain proteins or fats (lipids). When these sugar molecules are attached to proteins, they form glycoproteins. Glycoproteins have various important functions within the body, like the development of the brain, and coordination, and are essential for the normal growth and function of coagulation, hormonal regulation and organs like the liver and heart. PMM2-CDG can affect virtually any part of the body, although most cases usually have an important neurological component. PMM2-CDG is associated with a broad and highly variable range of symptoms and can vary in severity from mild cases to severe with disabling or life-threatening symptoms. Most cases are apparent in infancy. PMM2-CDG is caused by mutations of the PMM2 (phosphomannomutase-2) gene and is inherited as an autosomal recessive condition (two copies of an abnormal gene product must be present in order for the disease or trait to develop. Available treatments Effective treatment for PMM2-CDG remains an unmet need. A potential path to therapy for PMM2-CDG is repurposing already approved drugs like epalrestat, which was found as a drug target in a worm model by drug screening. Why is this article important? It is important to share these perspectives so researchers, clinicians and other parents and patients can learn from each other’s journeys and, importantly, to highlight that you are not alone.