Cerebral folate deficiency (CFD) syndromes are defined as neuro-psychiatric conditions with low CSF folate and attributed to different causes such as autoantibodies against the folate receptor-alpha (FR) protein that can block folate transport across the choroid plexus, FOLR1 gene mutations or mitochondrial disorders.
While the FRα defect is a disorder of brain-specific folate transport accompanied with cerebral folate deficiency (CFD) causing progressive neurological symptoms, LAMM syndrome is a solely malformative condition, with normal physical growth and cognitive development.
Generation of autoantibodies against the folate receptor required to transport 5MTHF into CSF and mutations in the folate receptor 1 (FOLR1) gene have been reported to be causes of CFD.