Functional methionine synthase deficiency due to cblG disorder: a report of two patients and a review

Am J Med Genet. 1997 Sep 5;71(4):384-90. doi: 10.1002/(sici)1096-8628(19970905)71:4<384::aid-ajmg3>;2-u.


Functional methionine synthase deficiency due to abnormal methylcobalamin metabolism causes megaloblastic anemia, moderate to severe developmental delay, lethargy, and anorexia in association with homocystinuria. Patients with this disorder of cobalamin metabolism can be classified into two separate groups, cblE or cblG, primarily on the basis of complementation analysis with cultured skin fibroblasts. We describe two unrelated boys, ages 3 and 5 years, with the cblG defect in methylcobalamin synthesis. Both children presented with severe developmental delay, lethargy, anorexia, and megaloblastic anemia. The diagnosis of homocystinuria was delayed in each case due to difficulties with detection of small amounts of homocystine in physiologic samples. The clinical course of cblG disease is favorably altered by treatment with intramuscular hydroxycobalamin. Megaloblastosis in the presence of adequate supplies of cobalamin and folate in the blood must alert the clinician to the possibility of functional methionine synthase deficiency and should prompt a careful search for associated biochemical hallmarks, including homocystinuria/emia.

Publication types

  • Case Reports
  • Review

MeSH terms

  • 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / deficiency*
  • Anemia, Macrocytic / enzymology
  • Anemia, Macrocytic / genetics
  • Anemia, Megaloblastic / enzymology*
  • Anemia, Megaloblastic / genetics
  • Anorexia / genetics
  • Child, Preschool
  • Developmental Disabilities / enzymology
  • Developmental Disabilities / genetics*
  • Female
  • Fibroblasts
  • Genetic Complementation Test
  • Homocystine / blood
  • Homocystinuria
  • Humans
  • Male
  • Methionine / blood
  • Skin / enzymology
  • Vitamin B 12 / analogs & derivatives
  • Vitamin B 12 / metabolism


  • Homocystine
  • Methionine
  • mecobalamin
  • 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase
  • Vitamin B 12