MTHFR and hyperinsulinemic hypoglycemia, familial, 4: Elevated serum or plasma levels of homocysteine are theorized to be secondary to impairments in metabolism, including cystathionine-synthase (CBS) deficiency or methylenetetrahydrofolate reductase (MTHFR) deficiency, certain disease states such as diabetes, or dietary deficiencies [1,2,5,6].