Other Causes of Disordered Folate Metabolism

Serum folate levels have been found to be significantly reduced in patients with rheumatoid arthritis. In a study of 77 patients, 42 with rheumatoid arthritis and 35 with osteoarthritis, Sanderson (S36) found the serum folate to be lower in the group with rheumatoid arthritis to a significant degree 

Many patients with infection have a reduced serum level of folate, particularly those with chronic bacterial infections. However, the development of a megaloblastic anemia is uncommon and when it does occur is perhaps more often associated with the treatment. It is probable that the folate deficiency is the result of a combination of fiictors including poor dietary intake, low reserves, an increased demand due to an increased cell turnover, impaired absorption, vomiting, and impaired metabolism due to the toxic state of the patient (C17, M16, W25). Pyrexia may also inhibit the reduction of folate. Panders and Rupert (P13) found that if folic acid was incubated with a chicken liver enzyme preparation at an elevated temperature the reduction of folic acid to tetrahydrofolic acid was inhibited. 

Whether folate deficiency predisposes to infection is not clear. Certainly many folate-depleted patients develop infections and there is little doubt that infection tends to place fiirther demands on folate reserves. 

Patients with homozygous sickle cell disease (SS) had a mean serum folate of 5.8 JLg/liter compared with 7.2 p.g/liter in patients with sickle cell trait and 7.9 p.g/liter in healthy controls. However, there was no correlation between the serum folate and the hematocrit or reticulocyte count. Since reticulocytes may have a higher folate concentration than mature erythrocytes, Liu found that the erythrocyte folate, measured before and after removal of the reticulocytes, was a reliable indicator of the folate status in patients with sickle cell disease despite the variable degree of re-ticulocytosis. Using this technique only one of nine patients was found to have a low erythrocyte concentration of the vitamin. Treatment with fohc acid resulted in higher hematocrits in three of four patients with low serum and erythrocyte folate concentrations, but only one of 12 patients with a normal folate concentration showed any improvement when treated with folate. 

There appears to be an increased requirement for folate in some patients with sickle cell disease, but this depends on the degree of hemolysis present and many patients seem able to maintain a normal folate profile. 

---