Urinary formiminoglutamic acid in the megaloblastic anaemias associated with pregnancy and malnutrition.

The pathogenesis of many of the common forms of megaloblastic anaemia in malnourished populations is obscure. The aetiological factors and response to therapy vary in different geographical areas, and confusion has arisen by the retention of certain ambiguous terms. Thus "nutritional megaloblastic anaemia" is often really megaloblastic anaemia associated with pregnancy, and "tropical megaloblastic anaemia" merges with the sprue syndrome. The therapeutic use of large (pharmacological) doses of vitamin B12 or folic acid rather than small (physiological) doses has obscured the assessment of the primary deficiency on the basis of the haematological response to therapy. In the investigation of these megaloblastic anaemias there is need for the application of a sensitive and specific test of folic-acid deficiency. In this respect reports of the measurement of urinary formiminoglutamic acid (Figlu) following a histidine load in humans deficient in folic acid are promising (Luhby et al. 1959; Spray and Witts, 1959; Kohn et al., 1961). In the South African Bantu both anaemia and malnutrition are common. Megaloblastic anaemia in Bantu adults occurs most commonly after pregnancy (Cassel and Metz, 1958), and about half of this group of patients show clinical evidence of malnutrition. The condition appears to differ from the pregnancy megaloblastic anaemias seen in white populations in that it usually presents after pregnancy, anything up to one year after delivery, and occurs almost exclusively in lactating females. Serum-vitamin-B12 levels are usually within normal limits (Metz, 1958), while the plasma clearance of injected doses of folic acid is abnormally rapid (Metz et al., 1961) and a haematological response can be induced by small doses of folic acid (0.4 mg. daily) but not by doses of vitamin B,2 of less than 30 jig. daily (Stevens and Metz, 1962). Most of the evidence therefore points to this condition being due to folic-acid deficiency. This group of patients thus seemed suitable to assess the value of Figlu excretion following histidine loading as an index of folic-acid deficiency. Demonstration of urinary Figlu would also provide additional evidence of folic-acid deficiency in this syndrome.