Genetic causes of cerebral folate deficiency: clinical, biochemical and therapeutic aspects

Over the past decade, a syndrome consisting of low folate values in the cerebrospinal fluid (CSF) has been described. The syndrome has been associated with both genetic and acquired conditions that affect folate transport and metabolism and can result in severe neurological disorders. There is a wide range of underlying pathophysiological mechanisms, but a common feature in most patients is a good clinical response to folate therapy, especially when the syndrome is diagnosed early. In this review, we focus our attention on the genetic diseases leading to profound cerebral folate deficiency (CFD) and review current clinical, metabolic and therapeutic approaches.

► Cerebral folate deficiency is a cause of several severe neurological disorders.
► Cerebral folate deficiency has been associated with genetic and acquired diseases.
► A common feature in most patients is a good clinical response to folate therapy.
► White matter disturbances are commonly observed in patients.