Hematologic Disorders



Figure 15-1
Metabolism of homocysteine





  • Cystathione B synthase: using cofactor B6, catalyzes conversion of homocysteine into cystathione via trans-sulfuration


  • Methionine synthase: using cofactor B12, catalyzes conversion of homocysteine into methionine via remethylation


  • MTHFR: using cofactor folate, catalyzes transfer of methyl group from methyl-THF to homocysteine, ultimately producing methionine and THF



  • Mild-moderate homocysteinemia due to disturbances in metabolism leads to increased risk of thrombosis and stroke (arterial > venous) by disturbing endothelial function



    • Cystathione beta synthase deficiency: elevated homocysteine and accelerated atherosclerosis



      • Homozygous mutation: 20-fold increase in homocysteine


      • Heterozygous mutation: milder clinical picture


    • MTHFR gene mutation:



      • At least 40 mutations have been identified with hyperhomocysteinemia


      • Impaired MTHFR activity leads to impaired conversion of homocysteine to methionine


      • Mutations in this gene also associated with anencephaly and spina bifida


    • Deficiencies in B12, B6, and folate


    • B6, folic acid, and B12 supplementation is associated with reduction in serum homocysteine levels





    • Homocystinuria : rare, AR, significant elevations of homocysteine in blood and urine leading to mental retardation and skeletal deformities





        Platelet Disorders




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        Oct 7, 2017 | Posted by in NEUROLOGY | Comments Off on Hematologic Disorders

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