Investigation of the Defect in a Variant of Hereditary Methemoglobinemia

1. Further evidence has been presented to confirm the fact that the methemoglobin found in a new variant of hereditary methemoglobinemia was normal methemoglobin.

2. The reduced glutathione content of the red cells of this variant was less than 50 per cent of normal.

3. The total glutathione and oxidized glutathione were proportionally deficient.

4. The low glutathione content did not result from abnormal degradation nor lack of adequate reducing mechanisms. The primary defect was considered to be one of inadequate glutathione synthesis.

5. Various enzymes were assayed, including the following: glucose 6-phosphate dehydrogenase, lactic acid dehydrogenase, triosephosphate dehydrogenase, glutathione reductase, glucose 6-phosphate dehydrogenase-glutathione reductase (coupled system) and catalase.

6. This variant of methemoglobinemia was considered to result from inadequate synthesis of glutathione. The deficiency of this essential co-factor apparently results in an impairment of triosephosphate dehydrogenase activity and consequently insufficient reduction of DPN, an essential component of the DPNH-dependent methemoglobin reductase.