HOMOCYSTINURIA

I. Biochemistry and pathophysiology

1. Homocysteine is an intermediate in metabolism of methionine, an essential amino acid. Methionine serves as a methyl group donator for the synthesis of a variety of important biochemical intermediates (purines, thymine, creatine, etc.) In donating its methyl group it is converted to S-adenosyl-homocysteine which is then converted to homocysteineserves 2 functions:

1. Can accept a methyl froup from folic acid to regenerate methionine (requires cobalamin)
2. Can be converted to cystathionine and then to cysteine, another amino acid (requires pyridoxine)

2. Hyperhomocystinemia and homocystinuria result from various enzyme defects (homozygotes > heterozygotes) or vitamin cofactor deficiencies
3. Hyperhomocysteinemia is strongly associated premature atherosclerosis and venous thromboembolism (Physician's Health Study, Framingham Heart Study) ; possibly also lens dislocation, skeletal abnormalities, and mental retardation

II. Treatment to reduce plasma homocysteine concentrations and hopefully avoid complications

1. Pyridoxine (B6)
2. Cobalamin (B12)
3. Folic Acid (B1)
4. Betaine (sometimes along with pyridoxine and folate)