Congenital Disorder of Glycosylation: Type Ia

Gene : PMM2

What is congenital disorder of glycosylation type IA?

Congenital disorder of glycosylation (CDG) is a group of inherited disorders caused by defects in glycosylation, the process of attaching sugars to proteins and lipids. The most common form of CDG is type IA, which is due to a deficiency in an enzyme named phosphomannomutase 2 and is sometimes referred to as phosphomannomutase 2 deficiency. CDG-IA affects the nervous system and many other organs and systems. Symptoms are highly variable, ranging from severe infantile multisystem involvement to mildly affected adults. Infants will typically have symptoms that include developmental delay, feeding difficulties, weak muscle tone, inverted nipples, and an abnormal distribution of fat. About 20 percent do not survive the first year of life due to severe infections or organ failure. The most severe form of CDG-IA appears in pregnancy, causing extreme fluid build-up in the body before birth. Babies are usually stillborn or die soon after birth. Individuals who survived infancy may have intellectual disability, inability to walk, joint and spine deformities, stroke like episodes, and absence of puberty for females. Currently there is no standard treatment for individuals with CDG-IA, but medical surveillance and care may help to improve some symptoms and overall condition of life. CDG-IA is caused by pathogenic variants in the PMM2 gene.

How is congenital disorder of glycosylation type IA inherited?

CDG-IA is inherited in an autosomal recessive manner. This type of inheritance requires the presence of two copies of a pathogenic variant in the gene for a person to have the genetic disease. Both parents must be carriers of a pathogenic variant in the gene in order to be at risk to have an affected child. The child must inherit a pathogenic variant from each carrier parent in order to be affected. There is a 1 in 4 chance that a baby will inherit two mutated copies of the gene and be affected when both parents are carriers.

What does it mean to be a carrier?

There are generally no signs or symptoms associated with being a carrier for CDG-IA. However, the risk to have a child affected with CDG-Ia is increased. Testing of reproductive partners is recommended for carriers of CDG-IA.

How common is congenital disorder of glycosylation type IA?

CDG-IA cases have been reported worldwide with more than 700 affected individuals reported to date. Approximately 50% of cases have been reported in individuals from Scandanavian countries. The disease is estimated to occur in 1 in 20,000 newborns for the European Caucasian population.

Family References and Resources
Clinician References
What is Analyzed?
  • Full gene sequencing
Affected Systems

Brain

Muscle

Bone

Heart

Liver

Metabolic

Immune

Carrier Rates
Ethnicity
Detection Rate
Carrier Frequency
Ashkenazi Jewish > 99% 1 in 57
General Population > 99% 1 in 198
Northern European Caucasian > 99% 1 in 60

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