Large erythrocytes in Down's syndrome: Their significance in relation to enzyme activity, gene dosage, and pyridoxine (B 6) metabolism

Abstract

A significant macrocytosis as reflected by increased packed cell volume and mean corpuscular volume, was found in a group of 12 institutionalized males with Down's syndrome compared to matched controls. There was no evidence of deficiency of vitamin B~, folic acid, pyridoxine, or iron to explain these differences. To determine whether the observed macrocytosis was attributable to a younger mean RBC age, erythrocyte glutamicoxaloacetic transaminase (EGOT) activity was measured. Also, because of previous reports of impaired tryptophane metabolism in Down's syndrome the question of B6 deficiency was investigated by the in vitro B,-stimulated EGOT; this was normal. However, base-line EGOT activity in the Down's syndrome group was significantly elevated when expressed in relation to red cells but not when related to hemoglobin concentration. This difference was present in both washed RBC and whole blood, although greater in the latter and presumably due to leukocytes with increased enzyme activity. Increased EGOT activity in association with macrocytosis suggests a younger mean cell age of the RBC population in Down's syndrome, and adds support to a similar explanation for the increased enzyme activity of WBC's in these patients, rather than the originally proposed gene dosage hypothesis. Failure to appreciate the macrocytosis in this condition may result in erroneous conclusions regarding the relation of RBC enzyme levels to gene dosage.