GM3 Synthase Deficiency

GM3 Synthase Deficiency is an autosomal recessive disease caused by a defect in the ST3GAL5 gene, which synthesizes GM3 ganglioside. This lipid is foundation of the entire ganglioside family of lipids and patients without thi lack any ganglioside in their cells. These lipids are important for brain development after birth and most children will show symptoms approximately 6 months after birth. Clinical symptoms include intellectual disability, seizures, hearing loss, and poor motor development. 

This disease was initially found in the Old Amish population, but has since been found in other ethnic groups including French, Pakistani, Italian, Saudi Arabian, Korean, African American, and Reunion Island families. 

Treatments are limited. Previous work has attempted to use an oral ganglioside replacement therapy and showed that while this could improve growth in infants, it has limited ability to enter the brain. This limitation is due to the blood-brain barrier, which is a layer of cells in the blood vessels of the brain that act as a gate to keep out molecules that normally are not found in the brain. Unfortunately, this protective effect also keeps out drugs that can potentially treat the disease. 

Recent work from the University of Massachusetts led by Dr. Guangping Gao, Dr. Dan Wang, and Dr. Kevin Strauss have resulted in a gene therapy that appears to be effective in mice. Further work is needed to bring this therapy in the clinic.