SRD5A3-congenital disorder of glycosylation (SRD5A3-CDG, formerly known as congenital disorder of glycosylation type Iq) is an inherited condition that causes neurological and vision problems and other signs and symptoms. The pattern and severity of this condition's features vary widely among affected individuals.

Individuals with SRD5A3-CDG typically develop signs and symptoms of the condition during infancy or early childhood. Most individuals with SRD5A3-CDG have intellectual disability, vision problems, unusual facial features, low muscle tone (hypotonia), and problems with coordination and balance (ataxia).

Vision problems in SRD5A3-CDG often include involuntary side-side movements of the eyes (nystagmus), a gap or hole in one of the structures of the eye (coloboma), underdevelopment of the nerves that carry signals between the eyes and the brain (optic nerve hypoplasia), or vision loss early in life (early-onset severe retinal dystrophy). Over time, affected individuals may develop clouding of the lenses of the eyes (cataracts) or increased pressure in the eyes (glaucoma).

Other features of SRD5A3-CDG can include skin rash, unusually small red blood cells (microcytic anemia), and liver problems.

SRD5A3-CDG is caused by variants (also known as mutations) in the SRD5A3 gene. This gene provides instructions for making the enzyme steroid 5 alpha-reductase 3, which facilitates the conversion of a compound called polyprenol to a compound called dolichol. This conversion is critical for a process called glycosylation, by which groups of sugar molecules (oligosaccharides) are attached to proteins. Glycosylation changes proteins in ways that are important for their functions.

Variants in the SRD5A3 gene typically lead to the production of abnormally small steroid 5 alpha-reductase 3 enzyme that either has no activity or is quickly broken down. Without any normal steroid 5 alpha-reductase 3 enzyme, dolichol production is impaired, and glycosylation cannot proceed normally. The signs and symptoms of SRD5A3-CDG are likely due to impaired glycosylation of proteins that are needed for the normal function of various organs and tissues.

Normal Function

The SRD5A3 gene provides instructions for making an enzyme called steroid 5-alpha reductase 3. This enzyme performs a chemical reaction that converts a compound called polyprenol into another compound called dolichol. Subsequently, another enzyme converts dolichol to dolichol phosphate. The production of dolichol phosphate is critical for a process called glycosylation, by which small chains of sugar molecules (oligosaccharides) are attached to proteins. Glycosylation changes proteins in ways that are important for their functions.

Dolichol phosphate is integral for the formation of the sugar chains that are attached to proteins during glycosylation. Individual sugars are added to dolichol phosphate to build the oligosaccharide chain. Once the chain is formed, it is transferred from dolichol phosphate to a specific site on the protein that needs to be glycosylated.

Health Conditions Related to Genetic Changes

SRD5A3-congenital disorder of glycosylation

More than 15 variants (also known as mutations) in the SRD5A3 gene have been found to cause SRD5A3-congenital disorder of glycosylation (SRD5A3-CDG). This condition primarily causes neurological and vision problems but can also cause other signs and symptoms.

Variants in the SRD5A3 gene generally lead to the production of abnormally small steroid 5 alpha-reductase 3 enzyme. This abnormal enzyme either has no activity or is quickly broken down. The lack of steroid 5 alpha-reductase 3 enzyme activity impairs the formation of dolichol, which also reduces dolichol phosphate production. As a result, glycosylation cannot proceed normally. The signs and symptoms of SRD5A3-CDG are likely due to impaired glycosylation of proteins that are needed for the normal function of various organs and tissues.

Other Names for This Gene

• FLJ13352
• SRD5A2L
• SRD5A2L1

Genomic Location

The SRD5A3 gene is found on chromosome 4.

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have variants. The parents of an individual with an autosomal recessive condition each carry one copy of the altered gene, but they typically do not show signs and symptoms of the condition.

SRD5A3-CDG appears to be a rare disorder; more than 40 affected individuals have been described in the scientific literature.