Impaired glycosphingolipid synthesis is a further cause of neuropathology: loss-of-function mutations in ST3GAL5 or B4GALNT1, which encode 2 key enzymes in ganglio-series glycosphingolipid synthesis (i.e., GM3 and GM2 synthases), cause neurodevelopmental regression (MIM #609056) and spastic paraplegia (MIM #609195), respectively (60–65). The gene discussed is ST3GAL5; the disease is Spastic paraplegia.