congenital disorder of glycosylation, PMM2-related

What is Congenital Disorder of Glycosylation, PMM2-related?

Congenital disorders of glycosylation (CDGs) are a group of inherited metabolic disorders caused by a disruption in the body's ability to attach sugar molecules to proteins (glycosylation) properly. There are many types of CDGs. CDG, PMM2-related is specifically caused by harmful genetic changes in the PMM2 gene. The condition affects many parts of the body and is highly variable between individuals (even those in the same family). Some harmful changes in the PMM2 gene are more severe and are incompatible with life, resulting in very early pregnancy loss. For infants who are born, the condition can generally be separated into three clinical phases as described below:

Infantile Multisystem Phase:

Common symptoms during infancy include low muscle tone (hypotonia); slow growth; a lack of reflexes; almond-shaped, crossed eyes; and abnormal genitals. Additional features can include inverted nipples, an unusual distribution of body fat, and a large forehead. Approximately 20% of infants with the disease die within the first year of life. For those who survive the first year, many develop a particular type of limited vision that progresses to blindness (retinitis pigmentosa) and wasting away of the cerebellum.

Late-Infantile and Childhood Phase:

This phase typically occurs between three to ten years. Symptoms include intellectual disability and delayed motor and speech development. Bone abnormalities, seizures, and stroke-like episodes may also occur.

Adult Stable Disability Phase:

This phase is typically between adolescence and early adulthood. Patients may develop an under-active thyroid (hypothyroidism), low blood sugar, and a decreased ability to form blood clots following an injury. Females with the disease often do not achieve sexual development. Additional features may include premature aging, enlarged liver and/or liver disease, heart problems, and kidney problems.

How common is CDG, PMM2-related?

CDG, PMM2-related, is the most common congenital disorder of glycosylation. The exact incidence is unknown but may be as common as 1 in 20,000 in some populations. It is most commonly reported in Denmark and other Scandinavian countries.

How is CDG, PMM2-related treated?

There is no cure for CDG, PMM2-related. Treatment for the condition is directed at managing the specific symptoms an individual has. This often means receiving care through a team of specialists that may include physicians, speech pathologists, occupational therapists, physical therapists, and social workers. Infants and children with CDG, PMM2-related will often benefit from receiving early intervention and other supportive services beginning at a young age. Adequate nutrition is required to assist with growth and development, and some individuals may require a feeding tube. Surgical or non-surgical measures may correct crossed eyes and ensure better vision. Medications may be prescribed to help control seizures. For individuals with an underactive thyroid gland, hormone therapy may be necessary. Wheelchairs and other movement aids can assist with mobility.

What is the prognosis for a person with CDG, PMM2-related?

Twenty percent of individuals with CDG, PMM2-related, die within the first year of life due to complications from the disease. Others may live into adulthood. Most are wheelchair-bound throughout their life. Some can speak and converse, although with some impairment. Most individuals with CDG, PMM2-related, cannot live independently but may accomplish specific tasks independently.