Congenital glycosylation disorders: how to identify the risk of transmission to offspring

Preconception genetic testing allows couples who are planning a pregnancy to check their health status and also the likelihood that they may transmit genetic diseases to their child. Some of the mutations that can be detected with this test could cause diseases that are defined as “rare,” in that they occur only in a few individuals in a given population.

I congenital disorders of glycosylation (CDG)

I Congenital disorders of glycosylation (CDG) fall among the rare diseases with heritable transmission. The estimated frequency of these disorders is one case per 50.000-100.000. They are diseases, of the type autosomal recessive, Are characterized by defects in the synthesis of glycoproteins, which are proteins bound to sugars.

Affected patients develop neurological problems and symptoms affecting several organs. 1

CDG syndromes develop when a mutation affects one of the genes

CDG syndromes develop when a mutation affects one of the genes that produce enzymes involved in metabolic processes, such as the phosphomannomutase. The most common form of CDG is precisely caused by a mutation on the gene PMM2 producing this enzyme, and it is named the CDG1a. CDG1a syndrome is the most frequent, diagnosed in 70% of CDG cases. Due to the mutation on PMM2, phosphomannomutase levels decrease.

1 CDG1a presents a extremely inhomogeneous clinical picture: some patients develop severe systemic pathology that is often fatal, while others have milder forms. 2

Generally, feeding disorders, vomiting, diarrhea, growth retardation, neuro-motor, ocular, psychomotor disorders, manifestation of stroke-like episodes and retinitis pigmentosa during early life and into adulthood are the symptoms characteristic of CDG syndromes. 2,3

Psychomotor retardation is definitely the most common symptom

Psychomotor retardation is definitely the most frequent symptom especially in early childhood. In severe cases, fetal hydrops at birth is reported. Approximately 20 percent of affected infants do not make it past one year of age due to complications in several vital organs. 4

Specific treatments aimed at ameliorating the effects of incorrect protein glycosylation are available for some forms of CDG. However, unfortunately, these approaches do not work for all forms. Available treatments for CDG1a syndrome, the most common and severe form, tend only to relieve symptoms. 5

To perform a diagnosis of CDG abnormalities in blood glycosylation of glycoproteins are sought by evaluating electrophoretic analysis of serum transferrin. Unfortunately, this test is not specific, because it does not distinguish the specific type of CDG. In fact, in case of a positive result, a specific search for mutations in the corresponding genes is required with a genetic testing. 4

Undergo a preconception genetic examination

Given the large number of heritable genetic diseases and also considering that these are often serious and rare diseases, it is understandable why many couples wishing to have a child decide to undergo preconception genetic testing. This type of test is safe and easy to perform: in fact, a simple blood draw by both members of the couple is enough. The Igea preconception testing allows one to know the likelihood of having children with a recessive genetic disease, just like CDG1a.

Consult your medical professional to plan the most appropriate reproductive pathway for your family.

Meanwhile, learn more about Igea, the preconception test from Genetic Source: www.sorgentegenetics.en

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