If FIGLU is excreted in excessive amounts after histidine loading it indicates a disturbance of folic acid metabolism. This is not necessarily due to a deficiency of folic acid—even a relative one due to the excessive utilisation of folic acid by abnormally active haematopoietic tissue or tumour tissue—but may be the result of a disturbance of folic acid metabolism by anticonvulsants, folic acid antagonists, impaired transferase activity, the unexplained disturbance of metabolism found in patients with megaloblastic anaemia of pregnancy, or some other cause.
Not all patients with megaloblastic anaemia and disturbed folic acid metabolism excrete excessive quantities of FIGLU. In some the excretion of FIGLU may be normal, and other workers have found the excretion of urocanic acid excessive in these patients. In some patients investigated in this study in whom the marrow showed megaloblastic erythropoiesis, the serum B12 level was normal and a satisfactory response followed the administration of folic acid, increased excretion of either FIGLU or urocanic acid could not be demonstrated. The nature of the metabolic abnormality in these patients is not understood.
Excessive excretion of urocanic acid after histidine loading was demonstrated in all patients with liver disease—all of whom were also anaemic. Two patients also excreted increased amounts of FIGLU. Other workers have found that non-anaemic patients with liver damage may excrete FIGLU and urocanic acid. These findings make the interpretation of excessive excretion of these substances in anaemic patients with liver disease difficult.
The histidine loading test does not distinguish between patients with Vitamin B12 deficiency and consequent disturbance of folic acid metabolism from patients with a normal serum B12 level and a disturbance of folic acid metabolism from some other cause.
Nearly all patients with a positive histidine loading test have evidence of megaloblastic erythropoiesis; however occasional patients may have normoblastic erythropoiesis. In these patients the histidine loading test may be more sensitive than marrow biopsy in revealing a disturbance of folic acid metabolism.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Baikie, A. G., Pirrie, R. (1956).Scot. Med. J., 1, 330.
Bakerman, H. A., Silverman, M., Daft, F. S. (1951).J. Biol. Chem., 188, 117.
Baldridge, R. C. (1958).J. Biol. Chem., 231, 207.
Carter, F. C., Schafner, G., Heller, P. (1960).Clin. Res., 8, 199.
Forshaw, J. (1963).Brit. Med. J., 2, 101.
Giles, C., Shuttleworth, E. M. (1958).Lancet, 2, 1341.
Girdwood, R. H. (1956).Quart. J. Med., 25, 87.
Girdwood, R. H., Lenman, J. A. R. (1956).Brit. Med. J., 1, 146.
Girdwood, R. H. (1959).Brit. Med. Bull., 15, 14.
de Gruchy, G. C. (1958).Clinical haematology in medical practice. Blackwell, London.
Hall, T. C. (1962).New Eng. J. Med., 266, 240.
Harper, H. A. (1961).Review of Physiological Chemistry (8th ed.). Lange Medical Publications, California.
Haurani, F. I., Wang, G., Tocantins, L. M. (1960).Blood, 16, 1546.
Herbert, V. (1959).The megaloblastic anaemias. Grune and Stratton.
Herbert, V., Baker, H., Frank, O., Pasher, I., Sobotka, H., Wasserman, L. R. (1960).Blood, 15, 228.
Huguley, C. M., Jr., Bain, J. A., Rivers, S. L., Scoggins, R. B. (1959).Blood, 14 615.
Knowles, J. P., Prankerd, T. A. J. (1962).Clin. Sci., 22, 233.
Kohn, J., Mollin, D. L., Rosenback, L. M. (1961).J. Clin. Path., 14, 345.
Merritt, A. D., Rucknagel, D. L. (1960).Clin. Res., 8, 213.
Mollin, D. L., Booth, C. C., Baker, S. J. (1957).Brit. J. Haemat., 3, 412.
Reisner, E. H. (1958).Blood, 13, 313.
This study is based on a communication to the Section of Pathology of the Royal Academy of Medicine in Ireland on 3rd April, 1963.
I should like to thank Dr. J. R. Mahon, Dr. P. J. Blaney and Dr. T. D. Hanratty for permission to study these patients under their care, and the Medical Research Council of Ireland for a gift of histidine.
About this article
Cite this article
Ryder, R.J.W., Path, M.C. An evaluation of the measurement of urinary formiminoglutamic acid excretion as an indication of disturbed folic acid metabolism. Ir J Med Sci 39, 403–411 (1964). https://doi.org/10.1007/BF02944738