Sphingolipids are a type of lipids that play diverse roles in cellular processes. Several different types of sphingolipids exist, with differing functions. The major difference between these different types of sphingolipids is due to modifications in their cerebroside moiety. The FA2H (Fatty Acid 2 Hydroxylase) protein is an enzyme that catalyzes one such modification (2-hydroxylation of the N-acyl chain in sphingolipids), thereby forming 2-hydroxysphingolipids. These 2-hydroxysphingolipids serve several functions, mostly in the brain.
Mutations in the FA2H gene have been found to cause leukodystrophy dysmyelinating with spastic paraparesis with or without dystonia (DLDSP). The disorder is characterized by progressive neurologic disease manifested by spasticity, disordered tonicity of muscle, and white matter degeneration. In addition, recently, mutations in the same gene have been found to be the cause of an autosomal recessive form of spastic paraplegia associated with a progressive course and features of leukodystrophy (SPG35).