PMM2-CDG, also known as congenital disorder of glycosylation type 1a (CDG-Ia), is a rare genetic disorder that affects the body's ability to produce certain proteins and sugars. It is caused by mutations in the PMM2 gene, which provides instructions for producing an enzyme called phosphomannomutase 2.
Genetic Mutations: The primary cause of PMM2-CDG is genetic mutations in the PMM2 gene. These mutations can be inherited from one or both parents or can occur spontaneously during the formation of reproductive cells or early embryonic development. The mutations disrupt the normal functioning of the PMM2 enzyme, leading to a deficiency or complete absence of its activity.
Enzyme Deficiency: The PMM2 enzyme plays a crucial role in a process called protein glycosylation. Glycosylation is the attachment of sugar molecules to proteins, which is essential for their proper structure and function. In PMM2-CDG, the deficiency of PMM2 enzyme activity impairs the glycosylation process, resulting in the production of abnormal proteins and sugars.
Metabolic Dysfunction: The disruption of protein glycosylation due to PMM2 gene mutations leads to metabolic dysfunction in various organs and tissues throughout the body. This dysfunction affects multiple systems, including the nervous system, liver, muscles, and immune system. The severity and specific symptoms can vary widely among individuals.
Autosomal Recessive Inheritance: PMM2-CDG follows an autosomal recessive pattern of inheritance. This means that an affected individual must inherit two copies of the mutated PMM2 gene, one from each parent, to develop the disorder. If both parents carry one copy of the mutated gene but do not have PMM2-CDG themselves, they are considered carriers and have a 25% chance of having an affected child with each pregnancy.
Genetic Heterogeneity: While PMM2 gene mutations are the most common cause of CDG-Ia, there are other genetic mutations that can also result in CDG. This genetic heterogeneity contributes to the wide range of symptoms and severity observed in individuals with CDG.
Early Diagnosis: PMM2-CDG is typically diagnosed in infancy or early childhood based on clinical symptoms, biochemical testing, and genetic analysis. Early diagnosis is crucial for implementing appropriate management strategies and interventions to improve the quality of life for affected individuals.
Treatment: Currently, there is no cure for PMM2-CDG. Treatment mainly focuses on managing the symptoms and complications associated with the disorder. This may involve a multidisciplinary approach, including dietary modifications, physical therapy, medications, and supportive care.