FURTHER-STUDIES ON ERYTHROCYTE THIAMIN TRANSPORT AND PHOSPHORYLATION IN 7 PATIENTS WITH THIAMIN-RESPONSIVE MEGALOBLASTIC-ANEMIA

Erythrocyte thiamin metabolism and transport were investigated in 7 pa tients from Brazil, Israel and Italy suffering from thiamin-responsive megaloblastic anaemia (TRMA) associated with diabetes mellitus and se nsorineural deafness. All patients discontinued thiamin therapy for 4- 7 days before the investigation. TRMA patients showed invariably reduc ed total thiamin levels in erythrocytes (percentage reduction compared with healthy controls, -46.8+/-3%; mean+/-SEM). The proportions of in dividual thiamin compounds, expressed as a percentage of total thiamin content, were within the normal range, whereas their absolute amounts were significantly decreased in the following order: thiamin monophos phate > thiamin pyrophosphate > thiamin. Thiamin pyrophosphokinase act ivity was also reduced as compared with controls (mean reduction+/-SEM , -25.9+/-1%). The saturable, specific component of thiamin uptake, wh ich normally prevails at physiological concentrations of thiamin (<2 m u mol/L), was absent in erythrocytes obtained from TRMA patients, whil e the non-saturable (diffusive) component of uptake was normally prese nt. These results confirm observations made previously in two patients and demonstrate that TRMA is consistently associated with a state of thiamin deficiency, which is presumably secondary to reduced thiamin c ellular transport and absorption (caused by lack of a membrane-specifi c carrier), and to impaired intracellular pyrophosphorylation.