SRD5A3
Name of Disorder

Steroid 5a-reductase type 3 congenital disorder of glycosylation (SRD5A3-CDG, also known as congenital disorder of glycosylation type Iq and SRD5A3 deficiency)

Symptoms

SRD5A3-CDG is a very rare inherited condition that affects multiple parts of the body. Individuals with SRD5A3-CDG typically develop signs and symptoms of the condition during infancy. All affected individuals present with impairments in balance and coordination due to neurological abnormalities. Frequent symptoms include variable combinations of other neurological abnormalities, including decreased muscle tone (hypotonia), a lack of muscle control or coordination of voluntary movements (ataxia), abnormalities of facial features (facial dysmorphism) and eye problems, including vision loss, nystagmus, coloboma, and underdevelopment of the optic disk/nerve. Affected individuals also often present with skin symptoms including hyperpigmentation, dry and loose skin, as well as increased thickening of the skin on the palms of hands and soles of feet (palmoplantar keratoderma). Symptoms that may develop over time are curving of the spine (kyphosis), cataracts and retinal degeneration (retinitis pigmentosa). Symptoms reported in a minority of patients include feeding problems, cardiac abnormalities and joint hypermobility.

Laboratory abnormalities may include elevated liver enzymes (serum transaminases), hypothyroidism, and abnormal clotting factor activities. There are 38 individuals with SRD5A3-CDG published in the medical literature.

Diagnosis

Diagnostic testing relies on testing the appropriate glycosylation of common proteins (one commonly used glycoprotein is transferrin). This can be tested by different methods in blood, but can also be normal in SRD5A3-CDG. The diagnosis is confirmed by genetic testing in blood. Individuals with SRD5A3-CDG have two faulty copies of the SRD5A3 gene.

Treatment and prognosis

To date, there is no curative treatment for SRD5A3-CDG. Treatment focuses on the management of symptoms through a combination of physical therapy, occupational therapy such as speech or vision therapy, and/or palliative measures. Prognosis is mainly determined by the nature and the degree of the brain and eye involvement. An individual in their 40s has been described in the medical literature.