Methylenetetrahydrofolate reductase deficiency: importance of early diagnosis.
Methylenetetrahydrofolate reductase deficiency is the most common inborn error of folate metabolism and should be suspected when homocystinuria is combined with hypomethioninemia. The main clinical findings are neurologic signs such as severe developmental delay, marked hypotonia, seizures, microcephaly, apnea, and coma. Most patients present in early life. The infantile form is severe, with rapid deterioration leading to death usually within 1 year. Treatment with betaine has been shown to be efficient in lowering homocysteine concentrations and returning methionine to normal, but the clinical response is variable. We report two brothers with methylenetetrahydrofolate reductase deficiency: the first was undiagnosed and died at 8 months of age from neurologic deterioration and apnea, while his brother, who was treated with betaine from the age of 4 months, is now 3 years old and has developmental delay.
Fattal-Valevski
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A
Institute for Child Development, Division of Pediatrics, Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Israel. afatal@post.tau.ac.il
Bassan
H
H
Korman
S H
SH
Lerman-Sagie
T
T
Gutman
A
A
Harel
S
S
D001622:Betaine / Q000627:therapeutic use; D002675:Child, Preschool; D003937:Diagnosis, Differential; D017809:Fatal Outcome; D005347:Fibroblasts / Q000378:metabolism; D005492:Folic Acid / Q000627:therapeutic use; D006397:Hematinics / Q000627:therapeutic use; D006710:Homocysteine / Q000097:blood / Q000187:drug effects / Q000652:urine; D006712:Homocystinuria / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics; D006720:Homozygote; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics; D008082:Lipotropic Agents / Q000627:therapeutic use; D008297:Male; D008715:Methionine / Q000097:blood; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D016896:Treatment Outcome
D006397:Hematinics; D008082:Lipotropic Agents; D006710:Homocysteine; D001622:Betaine; D005492:Folic Acid; D008715:Methionine; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)