What Your Test Results Mean:

Carriers typically show no symptoms of CDG-Ia; however, carriers are at an increased risk of having a child with CDG-Ia. Risk for the current or future pregnancies is dependent on your partner’s carrier status. Carrier testing of your partner is recommended in addition to consultation with a genetic counselor for more detailed risk assessment.

Disease Explained:

CDG-Ia is an inherited metabolic condition that is caused by abnormalities in phosphomannomutase-2, an enzyme that is important in glycosylation of proteins. Carbohydrate chains (glycosylation) are attached to many proteins as they are produced in the cell to control protein folding, localization, activity, and stability. These carbohydrate structures cannot
be formed properly without phosphomannomutase-2, leading to symptoms in multiple body systems. Symptoms of CDG-Ia usually present in the neonatal period and include global brain dysfunction, poor muscle tone, abnormal eye movement, and psychomotor retardation. Approximately 20% of infants with the disorder die within the first year of life due to severe infections, liver insufficiency, or cardiomyopathy. No treatment is currently available for this disorder.

How the Genetics Works:

CDG-Ia is an autosomal recessive disorder caused by pathogenic variants in the PMM2 gene. In general, individuals have two copies of the PMM2 gene. Carriers of CDG-Ia have a single variant in one copy of the PMM2 gene while individuals with CDG-Ia have variants in both copies of their genes, one inherited from each parent. Risk for two carriers to have a child with the disorder is approximately 1/3, due to preferential transmission of variants in the PMM2 gene.