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 patients from Brazil, Israel and Italy suffering from thiamin-responsive megaloblastic anaemia (TRMA) associated with diabetes mellitus and sensorineural deafness. All patients discontinued thiamin therapy for 4-7 days before the investigation. TRMA patients showed invariably reduced total thiamin levels in erythrocytes (percentage reduction compared with healthy controls, -46.8+/-3%; mean+/-SEM). The proportions of individual 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 monophosphate > thiamin pyrophosphate > thiamin. Thiamin pyrophosphokinase activity was also reduced as compared with controls (mean reduction+/-SEM, -25.9+/-1%). The saturable, specific component of thiamin uptake, which normally prevails at physiological concentrations of thiamin (<2 mu mol/L), was absent in erythrocytes obtained from TRMA patients, while the non-saturable (diffusive) component of uptake was normally present. 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 cellular transport and absorption (caused by lack of a membrane-specific carrier), and to impaired intracellular pyrophosphorylation.