SEVERE SELF-INJURIOUS BEHAVIORS AS MAIN CLINICAL MANIFESTATION OF A NEW FORM OF CEREBRAL FOLATE DEFICIENCY

Introduction: Cerebral Folate Deficiency (CFD) is a severe neurometabolic encephalopathy associated with low levels of 5-methyltetrahydrofolate (5MTHF) in cerebrospinal fluid (CSF) and normal systemic folate metabolism. We report on a new clinical variant of CFD. Case report: A 6 years old male with intellectual disability, hypotonia, acquired microcephaly and without epilepsy and autistic features came to our attention because of severe recurrent self-injuring behaviors (SIBs) (hitting his head by hands or feet with a rapid, stereotyped, compulsive limb movements), which were triggered by selective environmental changes or frustrating novelties. MRI was normal. He had a low cerebrospinal fluid (CSF) concentration of 5-methyltetrahydrofolate (5MTHF), increased CSF biopterin and normal values of peripheral blood folate. Mutations in Folate receptor 1 gene and the production of folate receptor blocking/binding autoantibodies were excluded. MTHFR gene sequencing and DHPR enzyme activity were normal. Lesch Nyhann, Rett and Angelman syndromes were excluded. Folate supplementation restored almost completely CSF folate without influencing either biopterin and biogenic amine concentrations or SIBs. Conclusions: Developmental delay, mental disability, acquired microcephaly, severe SIBs and undetectable 5MTHF in CSF with remarkable increase of biopterin are all hallmarks of this new condition associated to CFD. Epilepsy and autism spectrum disorder are notably absent.