Disorders of Cobalamin and Folate Metabolism

Cobalamin C deficiency (cblC) and related disorders of intracellular cobalamin metabolism may present at any time from the prenatal period through adolescence/adulthood and are due to deficiency of the cobalamin cofactors adenosylcobalamin and methylcobalamin. Chronic complications of cblC depend on the age at presentation and may include poor growth, renal dysfunction, neuropsychiatric manifestations, intellectual disability, strokes, progressive leukoencephalopathy and spinal cord degeneration, psychiatric manifestations and executive function deficits, and optic nerve and retinal anomalies. While less common than in isolated MMA, acute metabolic decompensation may occur in cblC patients due to accumulation of methylmalonic acid and associate metabolites and should be managed as in isolated MMA in conjunction with a metabolic consultant. The most common inborn error of folate (vitamin B9) metabolism relevant for adult patients is methylenetetrahydrofolate reductase (MTHFR) deficiency. Manifestations are primarily neurological, but the disorder may present in a substantial number of adults with psychiatric symptoms. Early recognition with adequate treatment is crucial.