Thiamine transport by erythrocytes and ghosts in thiamine‐responsive megaloblastic anaemia

Abstract

A 9-year study of thiamine metabolism and cellular transport was performed in two patients with thiamine-responsive megaloblastic anaemia associated with diabetes mellitus and sensorineural deafness, in their relatives, and in age-matched controls from the same area. The ratios between the content of thiamine and that of its phosphoesters in erythrocytes were within the normal range, whereas the absolute values of thiamine and thiamine compounds were reduced by about 40% as compared to controls. Thiamine pyrophosphokinase activity was about 30% lower than in controls. Thiamine treatment restored the levels of thiamine and thiamine compounds to normal values, whereas kinase was unaffected. Both the saturable (specific, predominant at low, less than 2 mumol/L, physiological concentrations of thiamine) and the non-saturable component of thiamine transport were investigated. Erythrocytes and ghosts from patients exhibited no saturable component, this abnormality being specific for the patients and not shared by their parents. It is concluded that the cells from thiamine-responsive megaloblastic anaemia patients contain low levels of thiamine compounds, probably due to their inability to take up and retain physiological concentrations of thiamine, as a result of the lack of the saturable, specific component of transport and reduced thiamine pyrophosphokinase.

Defective high-affinity thiamine transporter leads to cell death in thiamine-responsive megaloblastic anemia syndrome fibroblasts

“…Because thiamine concentrations in the intestinal lumen are low, Laforenza et al (8) propose that most thiamine is absorbed into the body by way of the high-affinity transporter. A similar pattern of thiamine uptake has also been seen in human erythrocytes (5,9,10). Whether the erythroid and intestinal thiamine uptake activities are identical is unknown.…”

“…Others (12,13) have cited mildly reduced levels of TPK activity as a primary defect. Poggi et al (5) first noted low TPP content of TRMA erythrocytes (∼50% of controls) and postulated that lack of a high-affinity thiamine transporter may be associated with the syndrome (5,9,10,14). The magnitude of the reported defect in thiamine uptake of erythrocytes was subtle, ∼60% of normal.…”

Obese individuals as thiamin storers

“…On repeated occasions our group studied the thiamin biochemical state in normal subjects: in their plasma, [12][13][14][15][16][17][18] cerebrospinal fluid (CSF), 13,14,18 erythrocytes, 8,[15][16][17][18][19][20][21] nervous tissue 7 and gut. 22 We have also investigated the thiamin state in neurological conditions (in the plasma and CSF of amyotrophic lateral sclerosis 14 ), in the erythrocytes of ataxias, 18 in haematologic syndromes (in the plasma and erythrocytes of thiamin-responsive megaloblastic anaemia 15,16,21 ), in metabolism (in the plasma and erythrocytes of diabetes insipidus, diabetes mellitus, optic atrophy and deafness or DIDMOAD syndrome 17 as well as in the plasma of diabetes 23 ) and toxic diseases (in the plasma and erythrocytes of alcoholism 13,19,20 ). Moreover, it is also well known that in a normal individual's plasma, we find T/TMP o 1 (in rats 12 and in man 13,18 ) and that in B 1 hypovitaminosis this ratio tends to become T/TMP ¼ 1.…”

Some Aspects of Thiamin Transport in Mammals

“…[5]. Erythrocytes (and ghosts) from these patients do not exhibit the saturable component of T uptake [6]. This abnormality appears to be specific because it was not shared by the parents of the patients (Fig.2).The absence of the saturable component of T transport, which is associated with reduced cellular T pyrophosphokinase activity, may explain the inability of these patients to maintain physiological tissue levels of T, a situation which is responsible for determining the clinical manifestations of the disease.…”