methaemoglobinaemia

Last edited 05/2023 and last reviewed 08/2023

Methaemoglobinaemia may be congenital or acquired. The iron in the haem is in the inactive (ferric) Fe3+ form instead of the normal (ferrous) Fe2+ form. Approximately 3% of haemoglobin is methaemoglobin in the healthy individual.

• methemoglobinemia is a condition characterized by increased quantities of hemoglobin in which the iron of heme is oxidized to the ferric (Fe3+) form (1)
  • methemoglobin is useless as an oxygen carrier and thus causes a varying degree of cyanosis

A sign of methaemoglobinaemia is the chocolate brown colour of blood.

The congenital form is an autosomal recessive condition caused by deficiency of cytochrome b5 reductase which converts methaemoglobin back to normal haemoglobin. Clinically, it is characterized by cyanosis

• typically methemoglobinemia due to NADH-cytochrome b5 reductase deficiency is inherited in an autosomal recessive fashion and so there may be no family history unless the patient is from a small community or their parents are fairly closely related (2)
• typically these children have clinically apparent methemoglobinemia, combined with severe neurological deficits, including profound cognitive impairment, growth retardation, microcephaly and dystonia (methemoglobinemia, type II) (2)

Acquired methaemoglobinaemia occurs when haemoglobin is reduced to methaemoglobin as may occur with large doses of prilocaine or application of silver sulphadiazine.

• critically ill hospitalized infants, inhaled nitric oxide therapy for pulmonary hypertension may lead to methemoglobinemia, necessitating regular monitoring (2)
  • methemoglobinemia may occur in the first few months of life in infants with marked metabolic acidosis, typically associated with sepsis or diarrhea and dehydration.

For all forms, methylene blue administered intravenously in a dose of 1mg/kg is an effective treatment.

Note that in normal oxygenation of haemoglobin, Fe2+ is not oxidised to Fe3+.

Reference:

• Pehman HU. Methemoglobinemia. West J Med. 2001 Sep;175(3):193-6. doi: 10.1136/ewjm.175.3.193. PMID: 11527852; PMCID: PMC1071541.
• Iolascon A, Bianchi P, Andolfo I, Russo R, Barcellini W, Fermo E, Toldi G, Ghirardello S, Rees D, Van Wijk R, Kattamis A, Gallagher PG, Roy N, Taher A, Mohty R, Kulozik A, De Franceschi L, Gambale A, De Montalembert M, Forni GL, Harteveld CL, Prchal J; SWG of red cell and iron of EHA and EuroBloodNet. Recommendations for diagnosis and treatment of methemoglobinemia. Am J Hematol. 2021 Dec 1;96(12):1666-1678. doi: 10.1002/ajh.26340. Epub 2021 Sep 23. PMID: 34467556; PMCID: PMC9291883