Congenital disorders of glycosylation (CDG) refer to a collection of over 130 rare genetic metabolic conditions caused by problems in the body’s glycosylation process. This process involves adding sugar building blocks, known as glycans, to proteins throughout the body, which is crucial for cell function. When there is a deficiency or absence of enzymes, CDG occurs.
These disorders affect multiple body systems, often leading to neurological issues, and typically become apparent during infancy. Although not all types of CDG are well-documented, a 2018 study estimated that 1 in 10,000 European and African American individuals are affected, based on predisposition to 53 different known genes. However, fewer than 100 cases have been recorded for most versions of CDG.
The more than 130 types of CDG are categorized into four groups: disorders of protein N-glycosylation, protein O-glycosylation, glycosphingolipid and GPI-anchor glycosylation, and multiple glycosylation and other pathways. N-glycosylation disorders are the most commonly diagnosed, and PMM2-CDG is the most prevalent type, caused by an enzyme malfunction in N-linked glycan processes.
CDG caused by O-glycosylation pathway issues includes some forms of muscular dystrophy. Disorders involving defects in glycosphingolipids and glycosylphosphatidylinositol anchors affect various bodily functions and manifest in diverse ways. Some CDG forms impact multiple glycosylation pathways, affecting both N-linked and O-linked processes.
Symptoms of CDG can vary greatly even among individuals with the same condition or from the same family but generally include neurological symptoms affecting the brain and spine. People with CDG may exhibit low muscle tone, developmental delays, cognitive impairments, and an underdeveloped cerebellum, among other health challenges. Additionally, they might experience abnormalities in the kidneys, liver, and skeletal system, as well as heart diseases like cardiomyopathy.
CDG is usually inherited from the parents. Most commonly, this occurs in an autosomal recessive pattern, where both parents carry but do not show symptoms of the genetic mutation. In other cases, it can be inherited in an autosomal dominant pattern, where just one parent carrying the gene can pass it on to the child. Sometimes, these genetic mutations arise spontaneously, without being inherited.
If both parents carry the gene for CDG, there is a 25% chance with each pregnancy that the child will have CDG. If a parent has a dominant form of CDG, the probability of passing it on to their child is 50%. But random mutations not inherited from the parents significantly lower the risk for siblings.
Due to the diverse symptoms, CDG is often misdiagnosed as conditions like cerebral palsy. Therefore, experts suggest that if multiple systems in the body are affected, CDG should be considered a possible diagnosis. Diagnosis involves a detailed medical history review and specific tests.
There is no cure for CDG, but treatments are available to manage symptoms and improve life quality, tailored to individual needs. Clinical trials may offer experimental treatment opportunities, and discussions with healthcare providers can provide more information.
Preventing CDG is challenging, especially with random mutations or unknown carrier status among parents. Genetic screening is available, although it may not cover all variations of CDG due to their diversity. Those affected or with a family history of CDG should seek support from networks like the CDG CARE Family Support Network for resources and community connections.
Life expectancy and quality of life for individuals with CDG depend on the type of CDG, symptom severity, and treatment response. For instance, 20% of children with PMM2-CDG, the most common type, die before age four, but survivors generally have good life expectancies. Speech, language, and cognitive abilities also vary, with some CDG types resulting in significant delays.
