Megaloblastic anemia and immune abnormalities in a patient with methionine synthase deficiency.
We report a case of methionine synthase deficiency associated with cellular immune deficiency discovered in a 14-year-old boy. Principal findings were: developmental delay, recurrent upper and lower respiratory tract infections, megaloblastic anemia, discovered at 3 months of age, unresponsive to cyanocobalamin and poorly responsive to folinic acid. Biochemical studies showed: an abnormal deoxyuridine suppression test despite normal serum folate, cobalamin and transcobalamin levels; a normal intracellular uptake of these two coenzymes; and an absolute requirement of methionine for fibroblast growth, suggestive of defective methionine synthesis. An absence of methionine synthase activity in the patient's bone marrow and a profound depression of this activity in lymphocytes and liver were found. Hypergammaglobulinemia with variable lymphopenia, depressed lymphocyte transformation after lectin or recall-antigen stimulation, defective delayed-type hypersensitivity and decreased natural killer activity were noted as well. The patient died at the age of 14.
Zittoun
J
J
Laboratoire Central d'Hématologie-Immunologie, Hôpital Henri Mondor, Creteil.
Fischer
A
A
Marquet
J
J
Pérignon
J L
JL
Lagrue
A
A
Griscelli
C
C
D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000172:deficiency* / Q000378:metabolism; D000293:Adolescent; D000748:Anemia, Macrocytic / Q000201:enzymology*; D000749:Anemia, Megaloblastic / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics; D002675:Child, Preschool; D003857:Deoxyuridine; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics; D007223:Infant; D007239:Infections / Q000209:etiology; D008297:Male; D008780:Methyltransferases / Q000172:deficiency*
D008780:Methyltransferases; D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; D003857:Deoxyuridine