Thiamine-responsive megaloblastic anemia

Apart from children with thiamin-responsive maple symp urine disease (Section 6.3.1.4) and thiamin-responsive megaloblastic anemia (Section 6.2), there are no established pharmacological uses of thiamin other than the treatment of deficiency. Because of the neurological involvement in thiamin deficiency, the vitamin has been used in nerve tonics, although there is no evidence that it has any effect except in cases of deficiency. 

Neufeld EJ, Fleming JC, Tartaglini E, and Steinkamp MP (2001) Thiamine-responsive megaloblastic anemia syndrome a disorder of high-affinity thiamine transport. Blood Cells Molecules and Diseases 27, 135-8. 

Raz T, Labay V, Baron D, Szargel R, Anbinder Y, Barrett T et al. The spectrum of mutations, including four novel ones, in the thiamine-responsive megaloblastic anemia gene SLC19A2 of eight families. Hum Mutat 2000 16 37-42. 

SLC19 Folate/thiamine transporter 3 Methotrexate Thiamine-responsive megaloblastic anemia... 

Genetic defects of the tissue thiamin transport protein and thiamin pyrophosphokinase cause megaloblastic anemia, presumahly as a result of impaired synthesis of pentoses for DNA synthesis from low activity of trans-ketolase (Section 6.3.2). In many cases, this megaloblastic anemia is thiamin-responsive, suggesting that the defect must be because of low af nity of either the transport protein or thiarnin pyrophosphokinase for its substrate (Neufeld et al., 2001). 

Four inherited disorders responsive to treatment with pharmacological doses of thiamine are summarized in Table 38-1. However, at least for megaloblastic anemia and maple syrup urine disease, more nonresponsive than responsive cases are known. Since thiamine is promptly excreted in the urine, excessive intake is not associated with toxicity. 

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