Congenital disorders of glycosylation (CDG) are a group of rare disorders that are caused by a breakdown in glycosylation. Glycosylation is a routine process carried out by cells where sugars are built and added to proteins or lipids. These sugars are important because they contribute to numerous cellular functions. Hence, disorders arising as a result of improper glycosylation can result in adverse physiological outcomes.
SRD5A3-CDG is one of 150 (and counting) ultra-rare CDG that causes developmental delays and problems with vision. The SRD5A3 gene encodes the polyprenol reductase enzyme which helps produce dolichol, a molecule essential for the eventual glycosylation of various proteins. Therefore, mutations in the SRD5A3 gene lead to defective proteins in the body, and the consequent symptoms.
As of 2018, there were atleast 20 reported cases of SRD5A3-CDG. While the exact number of patients worldwide is unknown, most cases have been of South Asian or Middle Eastern Descent.
Click here to learn about what you can do to be in the best position to take care of a loved one living with this condition.
The type and severity of symptoms vary greatly between different patients, even if they are diagnosed with the same condition. There are only a few documented cases of SRD5A3-CDG in the world, and symptoms all vary depending on the type of mutation. However, you may use our resource to gauge the severity and variability of symptoms your child may face.
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.
As mentioned in the Symptoms, Diagnosis, and Treatments section, while there are 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.