Summary
A 16-year-old Japanese girl with 5,10-methylenetetrahydrofolate reductase deficiency showed peripheral neuropathy. There were no significant responses to vitamin B6, vitamin B12 or folate, given alone or in combination. With the addition of betaine monohydrate, she has been free from gait disturbance and muscle weakness. The concentration ofS-adenosylmethionine in cerebrospinal fluid, which was undetectable before receiving betaine monohydrate, increased to about the normal level 24 months after treatment with betaine monohydrate.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Allen RJ, Wong P, Rothenberg SP, Dimauro S, Headington JT (1980) Progressive neonatal leukoencephalo-myopathy due to absent methylenetetrahydrofolate reductase, responsive to treatment.Ann Neurol 8: 211.
Beckman DR, Hoganson G, Berlow S, Gilbert EF (1987) Pathological findings in 5,10-methylenetetrahydrofolate reductase deficiency.Birth Defects 23: 47–64.
Brandt NJ, Christensen E, Skouby F, Djerne B (1986) Treatment of methylene tetrahydrofolate reductase deficiency from the neonatal period. The Society for the Study of Inborn Error of Metabolism, 24th Annual Symposium, Amersfoort, The Netherlands, 9–12 Sept. 22.
Clayton PT, Smith I, Harding B, Hyland K, Leonard JV, Leeming RJ (1986) Subacute combined degeneration of the cord, dementia and Parkinsonism due to an inborn error of folate metabolism.J Neurol Neurosurg Psychiatr 49: 920–927.
Duchen LW, Jacobs JM (1984) Nutritional deficiencies and metabolic disorders. In Adams JH, Corselis JAN, Duchen LW, eds.Greenfield's Neuropathology, 4th edn. London: Edward Arnold, 573–626.
Erbe RW (1979) Genetic aspects of folate metabolism.Adv Hum Genet 9: 293–354.
Erbe RW (1986) Inborn errors of folate metabolism in folates and pterins. In Blakley RL, Whitehead VM, eds. Folates and Pterins: Nutritional, Pharmacological and Physiological Aspects, Vol. 3, p. 413. New York: Wiley.
Freeman JM, Finkelstein JD, Mudd SH (1975) Folate-responsive homocystinuria and schizophrenia. A defect in methylation due to deficient 5,10-methylenetetrahydrofolate reductase activity.N Engl J Med 292: 491–496.
Harpey JP, Rosenblatt DS, Cooper BA, Le Moel G, Roy C, Lafourcade J (1981) Homocystinuria caused by 5,10-methylenetetrahydrofolate reductase deficiency: A case in an infant responding to methionine, folinic acid, pyridoxine, and vitamin B12 therapy.J Pediatr 98: 275–278.
Haworth JC, Dilling LA, Surtees RAH et al (1993) Symptomatic and asymptomatic methylenetetrahydrofolate reductase deficiency in 2 adult brothers.Am J Med Genet 45: 572–576.
Holme E, Kjellman B, Ronge E (1989) Betaine for treatment of homocystinuria caused by methylene tetrahydrofolate reductase deficiency.Arch Dis Child 64: 1061–1064.
Hyland K, Smith I, Bottiglieri T et al (1988) Demyelination and decreasedS-adenosylmethionine in 5,10-methylenetetrahydrofolate reductase deficiency.Neurology 38: 459–462.
Kang S-S, Wong PWK, Susmano A, Sora J, Norusis M, Ruggie N (1991) Thermolabile methylenetetrahydrofolate reductase: an inherited risk factor for coronary artery disease.Am J Hum Genet 48: 536–545.
Mudd SH, Uhlendorf BW, Freeman JM, Finkelstein JD, Shih VE (1972) Homocystinuria associated with decreased methylenetetrahydrofolate reductase activity.Biochem Biophys Res Commun 46: 905–912.
Narisawa K, Wada Y, Sato T et al (1977) Infantile type of homocystinuria withN 5,10-methylenetetrahydrofolate reductase defect.Tohoku J Exp Med 121: 185–194.
Nishimura M, Yoshino K, Tomita Y et al (1985) Central and peripheral nervous system pathology of homocystinuria due to 5,10-methylenetetrahydrofolate reductase deficiency.Pediatr Neurol 1: 375–378.
Rosenblatt DS (1989) Inherited disorders of folate transport and metabolism. In Scriver CR, Beaudet AL, Sly WS, Valle D, eds.The Metabolic Basis of Inherited Disease, 6th edn. New York: McGraw-Hill, 2049–2064.
Rosenblatt DS, Erbe RW (1977a) Methylenetetrahydrofolate reductase in cultured human cells. I. Growth and metabolic studies.Pediatr Res 11: 1137–1140.
Rosenblatt DS, Erbe RW (1977b) Methylenetetrahydrofolate reductase in cultured human cells. II. Genetic and biochemical studies of methylenetetrahydrofolate reductase deficiency.Pediatr Res 11: 1141–1143.
Secrist JA, Barrio JR, Leonard NJ, Weber G (1972) Fluorescent modification of adenosinecontaining coenzymes. Biological activities and spectroscopic properties.Biochemistry 11: 3499–3506.
Sonoki S, Tanaka Y, Hisamatsu S, Kobayashi T (1989) High-performance liquid chromatographic analysis of fluorescsent derivatives of adenine and adenosine and its nucleotides. Optimization of derivatization with chloroacetaldehyde and chromatographic procedures.J Chromatogr 475: 311–319.
Wendel U, Bremer HJ (1984) Betaine in the treatment of homocystinuria due to 5,10-methylenetetrahydrofolate reductase deficiency.Eur J Pediatr 142: 147–150.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kishi, T., Kawamura, I., Harada, Y. et al. Effect of betaine onS-adenosylmethionine levels in the cerebrospinal fluid in a patient with methylenetetrahydrofolate reductase deficiency and peripheral neuropathy. J Inherit Metab Dis 17, 560–565 (1994). https://doi.org/10.1007/BF00711591
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00711591