TRAPPC11-CDG is a type of rare inherited disorder called Congenital Disorders of Glycosylation (CDG). It is caused by subunit 11 of the TRAPPC protein complex, TRAPPC11, not working properly. This protein complex is important for intracellular trafficking (transporting molecules within our cells).
Symptoms
The TRAPPC11 gene provides instructions for our bodies to make the TRAPPC11 protein, a subunit for a larger multi-protein complex that plays an important role in intracellular trafficking (transporting molecules within our cells). Pathogenic variants in the TRAPPC11 gene cause a spectrum of disease ranging from a limb girdle muscular dystrophy (LGMD) to developmental disability with muscle disease, movement disorder, and global developmental delay/intellectual disability, or a congenital muscular dystrophy. 54 individuals have been reported to have TRAPPC11-related conditions in the literature. They present with two main phenotypes: a slowly progressive limb girdle muscular dystrophy (weakness and muscle wasting in the muscles around the hips and shoulders) with or without global developmental delay/intellectual disability (12 individuals), or systemic involvement with a typical congenital disorder of glycosylation presentation, including short stature, global developmental delay/intellectual disability, microcephaly (small head size), hypotonia (low muscle tone), poor speech, seizures, movement disorder, scoliosis, liver disease, visual abnormalities, and cataracts (42 individuals). Individuals with the CDG presentation may have abnormalities on brain imaging including cerebral atrophy and/or cerebellar abnormalities.
Diagnosis
Individuals with TRAPPC11-CDG muscular dystrophy have two non-working copies of the TRAPPC11 gene. This can be identified through genetic testing in blood or saliva. Pathogenic variants in TRAPPC11 can lead to abnormal transferrin (CDT) pattern, indicating abnormal N- and O-glycosylation in blood. Not all patients have abnormalities by CDT testing.
Treatment and Prognosis
To date, there are no known specific treatment options for TRAPPC11-CDG. Treatment is aimed at the management of symptoms and the prevention of complications.