cerebral folate deficiency 2018-06-23T19:01:19Z true Cerebral folate deficiency is defined as a neurological syndrome associated with low CSF 5-methyltetrahydrofolate (5MTHF), the active folate metabolite, in the presence of normal folate metabolism outside the nervous system. Cerebral folate deficiency can result from either disturbed folate transport or from increased folate turnover within the central nervous system. MONDO:0100034 Cerebral folate deficiency is defined as a neurological syndrome associated with low CSF 5-methyltetrahydrofolate (5MTHF), the active folate metabolite, in the presence of normal folate metabolism outside the nervous system. Cerebral folate deficiency can result from either disturbed folate transport or from increased folate turnover within the central nervous system. Typical features manifest from 4 months of age, with irritability, sleep disturbance, developmental delay, cerebellar ataxia, spastic paraplegia, deceleration of head growth, progressive hearing and visual impairment, dyskinesia and epilepsy (seen in one third of children). Neuroimaging shows progressive atrophy and demyelination. Causes include mutations in receptor-mediated folate receptor protein 1 (FR1), folate antagonists (irreversible binding or antibodies that block folate binding to FR1) and other causes of functional impairment in FR1. Secondary forms of cerebral folate deficiency have been recognized during chronic use of anti-folate (including anti-seizure) medications and in various conditions such as Rett syndrome and Aicardi-Goutieres syndrome. Treatment is with folinic acid, to normalize CSF 5MTHF values. metabolic etiology