Name of disorder: STT3A-CDG (Congenital Disorder of Glycosylation Iw, STT3A-congenital disorder of glycosylation)
Symptoms: STT3A-CDG is an extremely rare inherited condition that affects multiple parts of the body. It can be inherited in an autosomal recessive pattern (both copies of the genes have changes for symptoms to develop) or an autosomal dominant pattern (only one copy of the gene has a change in order for symptoms to occur) depending on the specific change in the gene STT3. Individuals with the recessive form of the condition exhibit severe neurologic predominant symptoms including seizures, intellectual disability and global developmental delay, small head, excessive sleepiness, as well as poor growth, and bleeding and clotting issues. Individuals with the autosomal-dominant form of the condition exhibit variable features that can include variable intellectual disability, dysmorphic features, short stature, abnormal bone development, and muscle cramps. There are currently less than 10 individuals described in the literature with the autosomal recessive form of STT3A-CDG, and 16 individuals with the autosomal dominant form of STT3A-CDG.
Diagnosis: Diagnostic testing relies on testing the appropriate glycosylation of common proteins (one commonly used glycoprotein is transferrin), which can be done by different methods in blood. Genetic testing is needed to confirm the diagnosis. Individuals with the autosomal dominant form of STT3A-CDG have one faulty copy of the STT3A gene. It can be caused by a new genetic mutation in the affected individual but can also be inherited. Individuals with the autosomal recessive form of STT3A-CDG have two faulty copies of the STT3A gene, which are often inherited, one faulty copy from their mother and one from their father.
Treatment and Prognosis: To date, there are no curative treatment options available for STT3A-CDG. Treatment is aimed at the management of symptoms and the prevention of complications.
Long-term prognosis seems to be better in the autosomal dominant form of STT3A-CDG with the oldest reported affected individual age 55 in 2021. However, severity of symptoms can be significantly different between individuals. Individuals with autosomal recessive STT3A-CDG tend to have more severe symptoms but have also survived into adulthood. The oldest individual published was age 28 years in 2017.