pediatrics
Methionine Metabolism Disorders
Other forms of homocystinuria
Various defects in the remethylation process can result in homocystinuria. Defects include deficiencies of methionine synthase (MS) and MS reductase (MSR), delivery of methylcobalamin and adenosylcobalamin, and deficiency of methylenetetrahydrofolate reductase (MTHFR, which is required to generate the 5-methyltetrahydrofolate needed for the MS reaction). Because there is no methionine elevation in these forms of homocystinuria, they are not detected by neonatal screening. Clinical manifestations are similar to other forms of homocystinuria. In addition, MS and MSR deficiencies are accompanied by neurologic deficits and Megaloblastic Macrocytic Anemias . Clinical manifestation of MTHFR deficiency is variable, including intellectual disability, psychosis, weakness, ataxia, and spasticity. Diagnosis of MS and MSR deficiencies is suggested by homocystinuria and megaloblastic anemia and confirmed by DNA testing. Patients with cobalamin defects have megaloblastic anemia and methylmalonic acidemia. MTHFR deficiency is diagnosed by DNA testing. Treatment is by replacement of hydroxycobalamin 1 mg IM once a day (for patients with MS, MSR, and cobalamin defects) and folate in supplementation similar to characteristic homocystinuria. 