PMM2-CDG
Name of disorder PMM2-congenital disorder of glycosylation (PMM2-CDG, also known as congenital disorder of glycosylation type Ia)
Symptoms

PMM2-CDG is an inherited condition that affects many parts of the body. Individuals with PMM2-CDG typically develop signs and symptoms of the condition during infancy. Affected infants may have weak muscle tone, retracted (inverted) nipples, an abnormal distribution of fat, eyes that do not look in the same direction (strabismus), developmental delay, and a failure to gain weight and grow at the expected rate (failure to thrive). Infants with PMM2-CDG also frequently have an underdeveloped part of the brain (cerebellum) that coordinates movement. Laboratory abnormalities include elevated liver enzymes, abnormal coagulation factor activities and hormonal imbalance (low blood sugar, hypothyroidism, late orabsent puberty). Affected individuals may also experience stroke-like episodes that involve an extreme lack of energy (lethargy) and temporary paralysis. Recovery from these episodes usually occurs over a period of a few weeks to several months. Young individuals with PMM2-CDG who survive infancy may have moderate intellectual disability, and some are unable to walk independently.

During adolescence or adulthood, individuals with PMM2-CDG have reduced sensation and weakness in their arms and legs (peripheral neuropathy), an abnormal curvature of the spine (scoliosis), impaired muscle coordination (ataxia), thrombosis (blood clots in the deep veins), and some affected individuals have an eye disorder called retinitis pigmentosa that causes vision lossThere are more than 1000 PMM2-CDG patients published in the medical literature.

Diagnosis

Diagnostic testing relies on testing the appropriate glycosylation of common proteins (one commonly used glycoprotein is transferrin). This can be tested by different methods in blood. Measuring the activity of the enzyme protein, PMM2 is also possible in blood. The ultimate diagnosis is genetic testing in blood. Individuals with PMM2-CDG have two faulty copies of the PMM2 gene.

Treatment and prognosis

PMM2-CDG can be lethal in 20% of patients in the first 4 years of life. Individuals, who survive to childhood have a good life expectancy. The oldest PMM2-CDG patient is in her late 40s. There is no curative treatment for PMM2-CDG, treatment focuses on the treatment of symptoms and prevention of complications.

Several drugs are under investigation in preclinical research studies for the treatment of PMM2-CDG.