Denise
Moderator
Molecular Psychiatry (2013) 18, 369–381; doi:10.1038/mp.2011.175; published online 10 January 2012
Cerebral folate receptor autoantibodies in autism spectrum disorder
Cerebral folate deficiency (CFD) syndrome is a neurodevelopmental disorder typically caused by folate receptor autoantibodies (FRAs) that interfere with folate transport across the blood–brain barrier.
Autism spectrum disorders (ASDs) and improvements in ASD symptoms with leucovorin (folinic acid) treatment have been reported in some children with CFD. In children with ASD, the prevalence of FRAs and the response to leucovorin in FRA-positive children has not been systematically investigated.
In this study, serum FRA concentrations were measured in 93 children with ASD and a high prevalence (75.3%) of FRAs was found. In 16 children, the concentration of blocking FRA significantly correlated with cerebrospinal fluid 5-methyltetrahydrofolate concentrations, which were below the normative mean in every case.
Children with FRAs were treated with oral leucovorin calcium (2 mg kg−1 per day; maximum 50 mg per day). Treatment response was measured and compared with a wait-list control group. Compared with controls, significantly higher improvement ratings were observed in treated children over a mean period of 4 months in verbal communication, receptive and expressive language, attention and stereotypical behavior.
Approximately one-third of treated children demonstrated moderate to much improvement. The incidence of adverse effects was low. This study suggests that FRAs may be important in ASD and that FRA-positive children with ASD may benefit from leucovorin calcium treatment.
Given these results, empirical treatment with leucovorin calcium may be a reasonable and non-invasive approach in FRA-positive children with ASD. Additional studies of folate receptor autoimmunity and leucovorin calcium treatment in children with ASD are warranted.
Cerebral folate deficiency (CFD) syndrome is a recently described neurometabolic disorder characterized by low concentrations of 5-methyltetrahydrofolate (5MTHF) in the cerebrospinal fluid (CSF), despite normal systemic folate levels. CFD is believed to be caused by the impaired transport of folates across the blood–brain barrier. The first reported cases of CFD manifested severe neurodevelopmental symptoms including spastic paraplegia, cerebellar ataxia, dyskinesia, seizures, acquired microcephaly and developmental regression, which occurred as early as 4 months of age.1, 2 Central visual disturbances (optic atrophy and blindness) and hearing loss occurred after age 3 and 6 years, respectively, in some cases.
http://www.nature.com/mp/journal/v18...p2011175a.html
Cerebral folate receptor autoantibodies in autism spectrum disorder
Cerebral folate deficiency (CFD) syndrome is a neurodevelopmental disorder typically caused by folate receptor autoantibodies (FRAs) that interfere with folate transport across the blood–brain barrier.
Autism spectrum disorders (ASDs) and improvements in ASD symptoms with leucovorin (folinic acid) treatment have been reported in some children with CFD. In children with ASD, the prevalence of FRAs and the response to leucovorin in FRA-positive children has not been systematically investigated.
In this study, serum FRA concentrations were measured in 93 children with ASD and a high prevalence (75.3%) of FRAs was found. In 16 children, the concentration of blocking FRA significantly correlated with cerebrospinal fluid 5-methyltetrahydrofolate concentrations, which were below the normative mean in every case.
Children with FRAs were treated with oral leucovorin calcium (2 mg kg−1 per day; maximum 50 mg per day). Treatment response was measured and compared with a wait-list control group. Compared with controls, significantly higher improvement ratings were observed in treated children over a mean period of 4 months in verbal communication, receptive and expressive language, attention and stereotypical behavior.
Approximately one-third of treated children demonstrated moderate to much improvement. The incidence of adverse effects was low. This study suggests that FRAs may be important in ASD and that FRA-positive children with ASD may benefit from leucovorin calcium treatment.
Given these results, empirical treatment with leucovorin calcium may be a reasonable and non-invasive approach in FRA-positive children with ASD. Additional studies of folate receptor autoimmunity and leucovorin calcium treatment in children with ASD are warranted.
Cerebral folate deficiency (CFD) syndrome is a recently described neurometabolic disorder characterized by low concentrations of 5-methyltetrahydrofolate (5MTHF) in the cerebrospinal fluid (CSF), despite normal systemic folate levels. CFD is believed to be caused by the impaired transport of folates across the blood–brain barrier. The first reported cases of CFD manifested severe neurodevelopmental symptoms including spastic paraplegia, cerebellar ataxia, dyskinesia, seizures, acquired microcephaly and developmental regression, which occurred as early as 4 months of age.1, 2 Central visual disturbances (optic atrophy and blindness) and hearing loss occurred after age 3 and 6 years, respectively, in some cases.
http://www.nature.com/mp/journal/v18...p2011175a.html