Congenital disorders of glycosylation (CDG) are a group of rare disorders that are caused by a defects in glycosylation. Glycosylation is the process by which sugar ‘trees’ (called glycans) are built and attached to proteins or lipids. Sugars are important for the function of many proteins and lipids and every system in the body needs glycosylation to be healthy. Because of this, people with CDG often have many health problems that affect multiple body systems.
SRD5A3-CDG is one of 160 + different types of CDG. It causes developmental delays and problems with vision. The SRD5A3 gene provides instructions for making an enzyme, called polyprenol reductase, which helps produce dolichol – a molecule that is essential for proper glycosylation of proteins and lipids. Therefore, mutations in the SRD5A3 gene lead to defective proteins in the body, and the consequent symptoms.
SRD5A3-CDG may suspected at a young age in children who have vision problems, developmental delay, low muscle tone, and problems with balance and coordination. (Read more about common symptoms of SRD5A3-CDG here)
Diagnosis of SRD5A3-CDG is typically achieved through blood tests and genetic testing. A blood test called serum transferrin analysis is usually the first test performed in suspected cases of CDG as it can detect abnormal glycoslyation patterns of the transferrin protein. But as with most cases of CDG, genetic testing is required to obtain a definitive diagnosis.
As of 2022, 48 cases of SRD5A3-CDG have been reported in the medical literature. While the exact number of patients worldwide is unknown, many patients are of South Asian descent.
Visit the learn about what you can do to be in the best position to take care of a loved one living with SRD5A3-CDG.
The type and severity of symptoms vary greatly between different patients, even if they are diagnosed with the same condition. As only ~ 50 cases of SRD5A3-CDG have been documented worldwide, many of whom are still children, medical professionals do not yet know how symptoms change over time.
Generally, children with CDG are very sociable and cheerful, and with the right care you can improve their quality of life. Join our SRD5A3 Families Facebook group here to connect with other families.
Symptoms of CDG vary greatly between individuals, even within a singly characterized disorder such as SRD5A3-CDG, as the same gene (SRD5A3) can be affected by different mutations. The resulting complexity of symptoms means that there needs to be personalized treatments for these disorders. Current options include personalized therapy based on individual needs (speech therapy, physiotherapy, etc.) to improve quality of life. However, researchers are excited about the possibility of using induced pluripotent stem cells (iPSCs) to personalize drug treatment.
In short, patient derived cells can be induced into stem cells through a process called de-differentiation, with the advantage being that these stem cells have an identical genome to that of the individual. Since such a model is so personalized, the optimal supplements, drug treatments, and gene therapies that can specifically fix the pathways gone awry in the individual patient. Click here for a comprehensive and relevant list of literature pertaining to personalized medicine, and current attempts to study and treat CDG using such models.
Although there are currently no specific treatments available for SRD5A3-CDG, counselling can be provided once risk is identified at earlier stages. Specific symptoms, such as some of the eye problems (surgically) and coagulation disorders can also be treated. In general, care for CDG patients involves disease management through a combination of physical therapy, occupational therapy such as speech or vision therapy, and/or palliative measures
As this disease is caused by a single mutation, it is an attractive candidate for gene therapy. Coupled with advances in personalized medicine, there could definitely be a cure in the future. However, there is a lot of research that must be done before such a technology becomes approved. Donate here to help out the researchers working to cure SRD5A3-CDG.
