title: Symptomatic and asymptomatic methylenetetrahydrofolate reductase deficiency in two adult brothers.
abstract: We describe two brothers with 5,10-methylene tetrahydrofolate reductase (MTHFR) deficiency. The younger patient first developed limb weakness, incoordination, paresthesiae, and memory lapses at age 15 years, and by his early twenties he was wheelchair bound. His older brother remains asymptomatic at age 37 years. Both had homocystinuria and homocystinemia and low plasma levels of methionine. MTHFR activities in cultured skin fibroblasts of both patients were < 10% control and residual enzyme activities were markedly reduced on heating. The parents had intermediate enzyme activities and the reductase in the father (who had unexplained paraparesis and homocystinemia), but not in the mother, was also thermolabile. Both patients were treated with oral folate and betaine which improved, but did not totally correct, their biochemical abnormality. MTHFR deficiency should be considered in the differential diagnosis of unexplained neurologic disease in adolescents and adults.
authors.affiliation: Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Canada.
authors.forename: J C
authors.initials: JC
authors.lastname: Haworth
authors.forename: L A
authors.initials: LA
authors.lastname: Dilling
authors.forename: R A
authors.initials: RA
authors.lastname: Surtees
authors.forename: L E
authors.initials: LE
authors.lastname: Seargeant
authors.forename: H
authors.initials: H
authors.lastname: Lue-Shing
authors.forename: B A
authors.initials: BA
authors.lastname: Cooper
authors.forename: D S
authors.initials: DS
authors.lastname: Rosenblatt
mesh_terms: D000328:Adult; D001622:Betaine / Q000627:therapeutic use; D004795:Enzyme Stability; D005492:Folic Acid / Q000627:therapeutic use; D006711:Homocystine / Q000378:metabolism; D006801:Humans; D008297:Male; D008661:Metabolism, Inborn Errors / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D008715:Methionine / Q000097:blood; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D009422:Nervous System Diseases / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000172:deficiency*; D015493:Paraparesis, Tropical Spastic / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism
chemical_list: D001622:Betaine; D006711:Homocystine; D005492:Folic Acid; D008715:Methionine; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)