What are the types of hereditary methemoglobinemia due to NADH reductase deficiency?

Updated: Dec 09, 2018
  • Author: Mary Denshaw-Burke, MD, FACP; Chief Editor: Emmanuel C Besa, MD  more...
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Answer

There are four types of hereditary methemoglobinemias that are secondary to deficiency of NADH cytochrome b5 reductase, which is encoded by the CYB5R3 gene. All of them are autosomal recessive disorders. Heterozygotes have 50% enzyme activity and no cyanosis; homozygotes that have elevated methemoglobin levels above 1.5% have clinical cyanosis. The four types are as follows:

  • Type I – This is the most common variant, and the enzyme deficiency is limited to the erythrocytes causing cyanosis; cyanosis usually, but not always, develops during infancy [17]
  • Type II – Widespread deficiency of the enzyme occurs in various tissues, including erythrocytes, liver, fibroblasts, and brain; it is associated with severe CNS symptoms, including encephalopathy, microcephaly, hypertonia, athetosis, opisthotonos, strabismus, mental retardation, and growth retardation; cyanosis is evident at an early age
  • Type III – Although the hematopoietic system (platelets, RBCs, and white blood cells [WBCs]) is involved, the only clinical consequence is cyanosis
  • Type IV – Like type I, this type has isolated involvement of the erythrocytes but results in chronic cyanosis

Deficiency of NADPH-flavin reductase can also cause methemoglobinemia.


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