Congenital disorder of glycosylation type Ia (Congenital disorder of glycosylation type Ia) - Gen PMM2.
Congenital altered glycosylation type Ia (CDG-Ia), also known as deficiency phosphomannomutase-2, is a hereditary disease that affects many parts of the body. The type and severity of the problems associated with the disease vary widely among affected individuals, sometimes even between members of the same family.
Individuals with CDG-Ia often have signs and symptoms of the disease during childhood hypotonia, retracted nipples, abnormal fat distribution, strabismus, delayed development and stunted growth. Often these children also have an underdeveloped cerebellum. Sometimes, affected individuals have distinctive facial features that may include a high forehead, a triangular face, large ears and a thin upper lip. Additional symptoms may include seizures, pericardial effusion and blood clotting disorders. About 20% percent of affected children do not survive beyond the first year of life due to multiorgan failure. More severe cases of congenital altered glycosylation type Ia are characterized by fetal hydrops. Most babies with fetal hydrops are stillborn or die shortly after birth.
People with CDG-Ia who survive childhood can have moderate intellectual disability and inability to walk independently. Affected individuals may also present lethargy and temporary paralysis. Overall, the recovery of these episodes occurs over a few weeks to several months. During adolescence or adulthood, individuals with peripheral neuropathy, kyphoscoliosis, ataxia and contractures. Some affected individuals have an eye condition called retinitis pigmentosa that causes loss of vision. Women with CDG-Ia have hipergonadotrópico hypogonadism, which affects the hormones that direct coding sexual development. As a result, these women do not go through puberty. Meanwhile, affected males have normal puberty, but often have small testicles.
Congenital altered glycosylation type Ia (CDG-Ia), is due to mutations in the gene PMM2, located on the short arm of chromosome 16 (16p13). This gene encodes the enzyme phosphomannomutase (PMM), which is involved in glycosylation, by which, oligosaccharides bind to proteins. Glycosylation modifies proteins so they can make a greater variety of functions.
There are more than 100 mutations in the gene PMM2 in people with the disease. These mutations change the structure of the enzyme PMM different ways. However, all mutations seem to result in a reduction in enzyme activity. This decrease in activity of the enzyme PMM causes a deficiency of GDP-mannose into cells. As a result, not enough activated mannose to form oligosaccharides. Glycosylation can not be performed normally because incorrect oligosaccharides are encoded. Signs and symptoms in CDG-Ia are probably due to encoding glycosylated proteins incorrectly in many organs and tissues.
This disease is inherited in an autosomal recessive pattern, that is, both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.
Tests in IVAMI: in IVAMI perform detection of mutations associated with congenital altered glycosylation type Ia, by complete PCR amplification of exons PMM2 gene, and subsequent sequencing.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).