title: Further studies on erythrocyte thiamin transport and phosphorylation in seven patients with thiamin-responsive megaloblastic anaemia.
abstract: 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 mumol/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.
authors.affiliation: Institute of Human Physiology, University of Pavia, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Rindi
authors.forename: C
authors.initials: C
authors.lastname: Patrini
authors.forename: U
authors.initials: U
authors.lastname: Laforenza
authors.forename: H
authors.initials: H
authors.lastname: Mandel
authors.forename: M
authors.initials: M
authors.lastname: Berant
authors.forename: M B
authors.initials: MB
authors.lastname: Viana
authors.forename: V
authors.initials: V
authors.lastname: Poggi
authors.forename: A N
authors.initials: AN
authors.lastname: Zarra
mesh_terms: D000749:Anemia, Megaloblastic / Q000097:blood*; D001692:Biological Transport; D002648:Child; D002675:Child, Preschool; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D006801:Humans; D007223:Infant; D010766:Phosphorylation; D013831:Thiamine / Q000097:blood* / Q000627:therapeutic use
chemical_list: D013831:Thiamine