Elevation of total homocysteine in the serum of patients with cobalamin or folate deficiency detected by capillary gas chromatography-mass spectrometry.
Abstract
To determine if levels of serum total homocysteine are elevated in patients with either cobalamin or folate deficiency, we utilized a new capillary gas chromatographic-mass spectrometric technique to measure total homocysteine in the serum of 78 patients with clinically confirmed cobalamin deficiency and 19 patients with clinically confirmed folate deficiency. Values ranged from 11 to 476 mumol/liter in the cobalamin-deficient patients and 77 of the 78 patients had values above the normal range of 7-22 mumol/liter as determined for 50 normal blood donors. In the cobalamin-deficient patients, serum total homocysteine was positively correlated with serum folate, mean corpuscular volume, serum lactate dehydrogenase, serum methylmalonic acid, and the degree of neurologic involvement, and inversely correlated with platelets and hematocrit. In the folate-deficient patients, values for serum total homocysteine ranged from 17 to 185 mumol/liter and 18 of the 19 patients had values above the normal range. Some patients with pernicious anemia who were intermittently treated with cyanocobalamin were found to have elevated serum levels of total homocysteine while they were free of hematologic and neurologic abnormalities. The measurement of serum total homocysteine will help define the incidence of cobalamin deficiency and folate deficiency in various patient populations.
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- Dawson DW. Diagnosis of vitamin B12 deficiency. Br Med J (Clin Res Ed) 1984 Oct 13;289(6450):938–939.[PMC free article] [PubMed] [Google Scholar]
- Lindenbaum J. Status of laboratory testing in the diagnosis of megaloblastic anemia. Blood. 1983 Apr;61(4):624–627. [PubMed] [Google Scholar]
- Schilling RF, Fairbanks VF, Miller R, Schmitt K, Smith MJ. "Improved" vitamin B12 assays: a report on two commercial kits. Clin Chem. 1983 Mar;29(3):582–583. [PubMed] [Google Scholar]
- Magnus EM, Bache-Wiig JE, Aanderson TR, Melbostad E. Folate and vitamin B12 (cobalamin) blood levels in elderly persons in geriatric homes. Scand J Haematol. 1982 Apr;28(4):360–366. [PubMed] [Google Scholar]
- Nexø E. Variation with age of reference values for P-cobalamins. Scand J Haematol. 1983 May;30(5):430–432. [PubMed] [Google Scholar]
- Evans DL, Edelsohn GA, Golden RN. Organic psychosis without anemia or spinal cord symptoms in patients with vitamin B12 deficiency. Am J Psychiatry. 1983 Feb;140(2):218–221. [PubMed] [Google Scholar]
- Cole MG, Prchal JF. Low serum vitamin B12 in Alzheimer-type dementia. Age Ageing. 1984 Mar;13(2):101–105. [PubMed] [Google Scholar]
- Metz J, Kelly A, Swett VC, Waxman S, Herbert V. Deranged DNA synthesis by bone marrow from vitamin B-12-deficient humans. Br J Haematol. 1968 Jun;14(6):575–592. [PubMed] [Google Scholar]
- HERBERT V. Minimal daily adult folate requirement. Arch Intern Med. 1962 Nov;110:649–652. [PubMed] [Google Scholar]
- Savage D, Lindenbaum J. Anemia in alcoholics. Medicine (Baltimore) 1986 Sep;65(5):322–338. [PubMed] [Google Scholar]
- Vitamin B12 deficiency in strict vegetarians. N Engl J Med. 1978 Dec 7;299(23):1319–1320. [PubMed] [Google Scholar]
- Higginbottom MC, Sweetman L, Nyhan WL. A syndrome of methylmalonic aciduria, homocystinuria, megaloblastic anemia and neurologic abnormalities in a vitamin B12-deficient breast-fed infant of a strict vegetarian. N Engl J Med. 1978 Aug 17;299(7):317–323. [PubMed] [Google Scholar]
- Shipman RT, Townley RR, Danks DM. Homocystinuria, addisonian pernicious anaemia, and partial deletion of a G chromosome. Lancet. 1969 Sep 27;2(7622):693–694. [PubMed] [Google Scholar]
- Hollowell JG, Jr, Hall WK, Coryell ME, McPherson J, Jr, Hahn DA. Homocystinuria and organic aciduria in a patient with vitamin-B12 deficiency. Lancet. 1969 Dec 27;2(7635):1428–1428. [PubMed] [Google Scholar]
- Davis JR, Jr, Goldenring J, Lubin BH. Nutritional vitamin B12 deficiency in infants. Am J Dis Child. 1981 Jun;135(6):566–567. [PubMed] [Google Scholar]
- Hoey H, Linnell JC, Oberholzer VG, Laurance BM. Vitamin B12 deficiency in a breastfed infant of a mother with pernicious anaemia. J R Soc Med. 1982 Aug;75(8):656–658.[PMC free article] [PubMed] [Google Scholar]
- GRASBECK R, GORDIN R, KANTERO I, KUHLBACK B. Selective vitamin B12 malabsorption and proteinuria in young people. A syndrome. Acta Med Scand. 1960 Jul 15;167:289–296. [PubMed] [Google Scholar]
- Lampkin BC, Mauer AM. Congenital pernicious anemia with coexistent transitory intestinal malabsorption of vitamin B12. Blood. 1967 Oct;30(4):495–502. [PubMed] [Google Scholar]
- LAMBERT HP, PRANKERD TA, SMELLIE JM. Pernicious anaemia in childhood. A report of two cases in one family and their relationship to the aetiology of pernicious anaemia. Q J Med. 1961 Jan;30:71–90. [PubMed] [Google Scholar]
- Parry TE. Serum valine and methionine levels in pernicious anaemia under treatment. Br J Haematol. 1969 Mar;16(3):221–229. [PubMed] [Google Scholar]
- Levy HL, Mudd SH, Schulman JD, Dreyfus PM, Abeles RH. A derangement in B12 metabolism associated with homocystinemia, cystathioninemia, hypomethioninemia and methylmalonic aciduria. Am J Med. 1970 Mar;48(3):390–397. [PubMed] [Google Scholar]
- Goodman SI, Moe PG, Hammond KB, Mudd SH, Uhlendorf BW. Homocystinuria with methylmalonic aciduria: two cases in a sibship. Biochem Med. 1970 Dec;4(5):500–515. [PubMed] [Google Scholar]
- Mudd SH, Uhlendorf BW, Freeman JM, Finkelstein JD, Shih VE. Homocystinuria associated with decreased methylenetetrahydrofolate reductase activity. Biochem Biophys Res Commun. 1972 Jan 31;46(2):905–912. [PubMed] [Google Scholar]
- Freeman JM, Finkelstein JD, Mudd SH. Folate-responsive homocystinuria and "schizophrenia". A defect in methylation due to deficient 5,10-methylenetetrahydrofolate reductase activity. N Engl J Med. 1975 Mar 6;292(10):491–496. [PubMed] [Google Scholar]
- Scott CR, Hakami N, Teng CC, Sagerson RN. Hereditary transcobalamin II deficiency: the role of transcobalamin II in vitamin B 12 -mediated reactions. J Pediatr. 1972 Dec;81(6):1106–1111. [PubMed] [Google Scholar]
- Rosenblatt DS, Laframboise R, Pichette J, Langevin P, Cooper BA, Costa T. New disorder of vitamin B12 metabolism (cobalamin F) presenting as methylmalonic aciduria. Pediatrics. 1986 Jul;78(1):51–54. [PubMed] [Google Scholar]
- Corbeel L, Van den Berghe G, Jaeken J, Van Tornout J, Eeckels R. Congenital folate malabsorption. Eur J Pediatr. 1985 Mar;143(4):284–290. [PubMed] [Google Scholar]
- Stabler SP, Marcell PD, Podell ER, Allen RH, Lindenbaum J. Assay of methylmalonic acid in the serum of patients with cobalamin deficiency using capillary gas chromatography-mass spectrometry. J Clin Invest. 1986 May;77(5):1606–1612.[PMC free article] [PubMed] [Google Scholar]
- Stabler SP, Marcell PD, Podell ER, Allen RH. Quantitation of total homocysteine, total cysteine, and methionine in normal serum and urine using capillary gas chromatography-mass spectrometry. Anal Biochem. 1987 Apr;162(1):185–196. [PubMed] [Google Scholar]
- Marcell PD, Stabler SP, Podell ER, Allen RH. Quantitation of methylmalonic acid and other dicarboxylic acids in normal serum and urine using capillary gas chromatography-mass spectrometry. Anal Biochem. 1985 Oct;150(1):58–66. [PubMed] [Google Scholar]
- Wilcken DE, Gupta VJ, Reddy SG. Accumulation of sulphur-containing amino acids including cysteine-homocysteine in patients on maintenance haemodialysis. Clin Sci (Lond) 1980 May;58(5):427–430. [PubMed] [Google Scholar]
- Kang SS, Wong PW, Bidani A, Milanez S. Plasma protein-bound homocyst(e)ine in patients requiring chronic haemodialysis. Clin Sci (Lond) 1983 Sep;65(3):335–336. [PubMed] [Google Scholar]
- Finkelstein JD, Mudd SH. Trans-sulfuration in mammals. The methionine-sparing effect of cystine. J Biol Chem. 1967 Mar 10;242(5):873–880. [PubMed] [Google Scholar]
- Finkelstein JD, Martin JJ. Methionine metabolism in mammals. Distribution of homocysteine between competing pathways. J Biol Chem. 1984 Aug 10;259(15):9508–9513. [PubMed] [Google Scholar]
- Finkelstein JD, Martin JJ. Methionine metabolism in mammals. Adaptation to methionine excess. J Biol Chem. 1986 Feb 5;261(4):1582–1587. [PubMed] [Google Scholar]
- Wilcken DE, Reddy SG, Gupta VJ. Homocysteinemia, ischemic heart disease, and the carrier state for homocystinuria. Metabolism. 1983 Apr;32(4):363–370. [PubMed] [Google Scholar]
- Brattstrom LE, Hardebo JE, Hultberg BL. Moderate homocysteinemia--a possible risk factor for arteriosclerotic cerebrovascular disease. Stroke. 1984 Nov-Dec;15(6):1012–1016. [PubMed] [Google Scholar]
- Boers GH, Smals AG, Trijbels FJ, Fowler B, Bakkeren JA, Schoonderwaldt HC, Kleijer WJ, Kloppenborg PW. Heterozygosity for homocystinuria in premature peripheral and cerebral occlusive arterial disease. N Engl J Med. 1985 Sep 19;313(12):709–715. [PubMed] [Google Scholar]
- Frenkel EP. Abnormal fatty acid metabolism in peripheral nerves of patients with pernicious anemia. J Clin Invest. 1973 May;52(5):1237–1245.[PMC free article] [PubMed] [Google Scholar]
- Kishimoto Y, Williams M, Moser HW, Hignite C, Biermann K. Branched-chain and odd-numbered fatty acids and aldehydes in the nervous system of a patient with deranged vitamin B 12 metabolism. J Lipid Res. 1973 Jan;14(1):69–77. [PubMed] [Google Scholar]
- Scott JM, Dinn JJ, Wilson P, Weir DG. Pathogenesis of subacute combined degeneration: a result of methyl group deficiency. Lancet. 1981 Aug 15;2(8242):334–337. [PubMed] [Google Scholar]
- van der Westhuyzen J, van Tonder SV, Gibson JE, Kilroe-Smith TA, Metz J. Plasma amino acids and tissue methionine levels in fruit bats (Rousettus aegyptiacus) with nitrous oxide-induced vitamin B12 deficiency. Br J Nutr. 1985 May;53(3):657–662. [PubMed] [Google Scholar]
- van der Westhuyzen J, Fernandes-Costa F, Metz J. Cobalamin inactivation by nitrous oxide produces severe neurological impairment in fruit bats : protection by methionine and aggravation by folates. Life Sci. 1982 Nov 1;31(18):2001–2010. [PubMed] [Google Scholar]