FUNCTIONAL METHIONINE SYNTHASE DEFICIENCY DUE TO CBLG DISORDER - A REPORT OF 2 PATIENTS AND A REVIEW

Functional methionine synthase deficiency due to abnormal methylcobala min metabolism causes megaloblastic anemia, moderate to severe develop mental delay, lethargy, and anorexia in association with homocystinuri a, Patients with this disorder of cobalamin metabolism can be classifi ed into two separate groups, cb1E or cb1G, primarily on the basis of c omplementation analysis with cultured skin fibroblasts, We describe tw o unrelated boys, ages 3 and 5 years, with the cb1G defect in methylco balamin synthesis, Both children presented with severe developmental d elay, lethargy, anorexia, and megaloblastic anemia, The diagnosis of h omocystinuria was delayed in each case due to difficulties with detect ion of small amounts of homocystine in physiologic samples, The clinic al course of cb1G disease is favorably altered by treatment with intra muscular hydroxycobalamin. Megaloblastosis in the presence of adequate supplies of cobalamin and folate in the blood must alert the clinicia n to the possibility of functional methionine synthase deficiency and should prompt a careful search for associated biochemical hallmarks, i ncluding homocystinuria/emia. (C) 1997 Wiley-Liss, Inc.