Clinical, fluorine-18 labeled 2-fluoro-2-deoxyglucose positron emission tomography of the brain, MR spectroscopy, and therapeutic attempts in methylenetetrahydrofolate reductase deficiency

The cases of three infants, two Saudi and one Bahraini, with methylenetetra hydrofolate reductase (MTHFR) deficiency are reported. They presented in th e neonatal period with lethargy, poor feeding, hypotonia, and frequent apne as. Tandem mass spectrometry (MS/MS) of a blood spot indicated very low met hionine level and of urine revealed high homocysteine. The diagnosis was co nfirmed by demonstrating severe deficiency of MTHFR in the cultured skin fi broblast. All patients were treated with folinic acid, vitamin B-12, betain e, and methionine, with good initial response to the therapy. In two patien ts, the diagnosis was late and their disease was severe, resulting in neuro logical crippling. However, in the third patient, who was diagnosed and tre ated early, the current neurological status is normal. In her case, at 1 mo nth of age, the brain FDG PET scan documented very faint cerebral and cereb ellar cortical activities. After 5 months of intensive therapy, that includ ed 200-600 mg/kg per day methionine, she had a dramatic clinical and bioche mical recovery as well as a parallel improvement in FDG PET. Brain MR spect roscopy indicated normal neuronal glial and myelin markers for her age. We conclude that the functional changes confirmed by the FDG PET study were be tter correlated with the clinical course of the patient and adequately moni tored the response to therapy. This disease warrants early detection throug h neonatal screening program, since the beneficial effect of early administ ration of adequate therapy with combined use of betaine and a high dose of methionine is rewarding and may be the treatment of choice for MTHFR defici ency. (C) 1999 Elsevier Science B.V. All rights reserved.