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More widespread use of exome and genome sequencing combined with improved data sharing platforms have led to the characterization of “new” neurometabolic disorders. This review provides an overview of the folate and polyamine metabolic pathways, summarizes the established disorders, and highlights two recently described disorders of folate and polyamine metabolism. 5,10-methenyltetrahydrofolate synthetase (MTHFS) deficiency is an emerging disorder of folate metabolism that manifests with neurodevelopmental abnormalities, epilepsy, spasticity, short stature, microcephaly, cerebral hypomyelination, and cerebellar atrophy. Cerebrospinal fluid 5-MTHF levels are reduced, with normal peripheral folate levels. MTHFS deficiency may be amenable to treatment with 5-methyltetrahydrofolate, whereas folinic acid, used in other forms of cerebral folate deficiency, may be contraindicated. There are two inborn errors of polyamine metabolism in humans described to date, including the neurodevelopmental disorder Snyder-Robinson syndrome and the recently described ODC1 disorder. ODC1 disorder is associated with a recognizable phenotype, including neurodevelopmental and behavioral abnormalities, macrocephaly, alopecia, craniofacial dysmorphisms, and MRI abnormalities. The pathogenic variants in this gene described to date appear to confer a gain-of-function effect. It is yet to be determined if there is an effective targeted treatment for ODC1 disorder.


cerebral folate deficiency, folate metabolism, 5,10-methenyltetrahydrofolate synthetase (MTHFS) deficiency, polyamine metabolism, ornithine decarboxylase 1 (ODC1) deficiency

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How to Cite
Rodan, L. (2022). Update in pediatric neurometabolic disorders: folate and polyamine metabolism. Journal of the International Child Neurology Association, 1(1).


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