Skip to Main Content

Key Features

  • Consider in a child of any age with a marfanoid habitus, dislocated lenses, or thrombosis

  • Diagnosis is suggested by elevated total homocysteine and methionine

  • Newborn screening allows early diagnosis and treatment resulting in a normal outcome

  • Most often due to deficiency of cystathionine β-synthase (CBS)

  • May also be due to deficiency of methylenetetrahydrofolate reductase (MTHFR) or to defects in the biosynthesis of methyl-B12, the coenzyme for methionine synthase

  • All inherited forms of homocystinuria are autosomal recessive traits

Clinical Findings

  • Mental retardation in about 50% of patients with untreated CBS

  • Most patients have arachnodactyly, osteoporosis, and a tendency to develop dislocated lenses and thromboembolic phenomena

  • Mild variants of CBS deficiency present with thromboembolic events

  • Patients with severe remethylation defects usually exhibit failure to thrive and a variety of neurologic symptoms, including

    • Brain atrophy

    • Microcephaly

    • Hydrocephalus

    • Seizures in infancy and early childhood


  • Diagnosis is made by demonstrating elevated total serum homocysteine or by identifying homocystinuria in a patient who is not severely deficient in vitamin B12

  • Plasma methionine levels

    • Usually high in patients with CBS deficiency

    • Often low in patients with remethylation defects

  • Cystathionine levels are low in CBS deficiency

  • When the remethylation defect is due to deficiency of methyl-B12, megaloblastic anemia or hemolytic uremic syndrome may be present and an associated deficiency of adenosyl-B12 may cause methylmalonic aciduria

  • Mutation analysis or studies of cultured fibroblasts can make a specific diagnosis


  • Large oral doses of pyridoxine effective in about 50% of patients with CBS deficiency

  • Pyridoxine nonresponders are treated with dietary methionine restriction and oral administration of betaine, which increases methylation of homocysteine to methionine and improves neurologic function

  • Early treatment prevents mental retardation, lens dislocation, and thromboembolic manifestations

  • Large doses of vitamin B12 (eg, 1–5 mg hydroxocobalamin administered daily intramuscularly or subcutaneously) are indicated in some patients with defects in cobalamin metabolism

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.