Chapter 37 - Disorders of cobalamin and folate metabolism

Summary

Genetically determined and acquired disorders leading to relative cobalamin deficiency result in hematologic changes characterized by megaloblastic anemia. Acquired disorders of cobalamin deficiency occur far more frequently than genetically determined disorders and often result in a variety of neurologic syndromes. Seizures are recognized as an uncommon manifestation of cobalamin deficiency, especially in adults. Early-onset cblC or cblD disorder, which results in both homocystinuria and methylmalonic aciduria, has been described in several reports to feature prominent seizures. Use of valproic acid, carbamazepine, and phenytoin has been shown in epileptic patients to lower serum cobalamin levels. Mutations affecting the proton-coupled folate transporter (PCFT) result in deficient uptake of folate at both the intestinal and choroid plexus levels and causes hereditary folate malabsorption. Neuroimaging studies detect non-specific cerebral atrophy and the intracranial, particularly occipital, calcifications noted especially in folate deficiency.