Methemoglobinemia, beta-globin type

Methemoglobinemia, beta-globin type is a condition that affects the function of red blood cells. Specifically, it alters a molecule called hemoglobin within these cells. Hemoglobin within red blood cells attaches (binds) to oxygen molecules in the lungs, which it carries through the bloodstream, then releases in tissues throughout the body. Instead of normal hemoglobin, people with methemoglobinemia, beta-globin type have an abnormal form called methemoglobin, which is unable to efficiently deliver oxygen to the body's tissues. In methemoglobinemia, beta-globin type, the abnormal hemoglobin gives the blood a brown color. It also causes a bluish appearance of the skin, lips, and nails (cyanosis), which usually first appears around the age of 6 months. The signs and symptoms of methemoglobinemia, beta-globin type are generally limited to cyanosis, which does not cause any health problems. However, in rare cases, severe methemoglobinemia, beta-globin type can cause headaches, weakness, and fatigue.

The incidence of methemoglobinemia, beta-globin type is unknown.

Methemoglobinemia, beta-globin type is caused by mutations in the HBB gene. This gene provides instructions for making a protein called beta-globin. Beta-globin is one of four components (subunits) that make up hemoglobin. In adults, hemoglobin normally contains two subunits of beta-globin and two subunits of another protein called alpha-globin. Each of these protein subunits is bound to an iron-containing molecule called heme; each heme contains an iron molecule in its center that can bind to one oxygen molecule. For hemoglobin to bind to oxygen, the iron within the heme molecule needs to be in a form called ferrous iron (Fe²⁺). The iron within the heme can change to another form of iron called ferric iron (Fe³⁺), which cannot bind oxygen. Hemoglobin that contains ferric iron is known as methemoglobin.

HBB gene mutations that cause methemoglobinemia, beta-globin type change the structure of beta-globin and promote the heme iron to change from ferrous to ferric. The ferric iron cannot bind oxygen and causes cyanosis and the brown appearance of blood.

Genetic Testing Information

• Genetic Testing Registry: Methemoglobinemia, beta-globin type

Genetic and Rare Diseases Information Center

• Hemoglobin M disease

Patient Support and Advocacy Resources

• National Organization for Rare Disorders (NORD)

Clinical Trials

• ClinicalTrials.gov

Catalog of Genes and Diseases from OMIM

• HEMOGLOBIN--BETA LOCUS; HBB

Scientific Articles on PubMed

• PubMed

• do Nascimento TS, Pereira RO, de Mello HL, Costa J. Methemoglobinemia: from diagnosis to treatment. Rev Bras Anestesiol. 2008 Nov-Dec;58(6):651-64. doi: 10.1590/s0034-70942008000600011. English, Portuguese. Citation on PubMed
• Melarkode K, Prinzhausen H. Hemoglobin M variant and congenital methemoglobinemia: methylene blue will not be effective in the presence of hemoglobin M. Can J Anaesth. 2008 Feb;55(2):129-30. doi: 10.1007/BF03016328. No abstract available. Citation on PubMed
• Percy MJ, McFerran NV, Lappin TR. Disorders of oxidised haemoglobin. Blood Rev. 2005 Mar;19(2):61-8. doi: 10.1016/j.blre.2004.02.001. Citation on PubMed
• Rehman HU. Methemoglobinemia. West J Med. 2001 Sep;175(3):193-6. doi: 10.1136/ewjm.175.3.193. No abstract available. Citation on PubMed or Free article on PubMed Central
• Skold A, Cosco DL, Klein R. Methemoglobinemia: pathogenesis, diagnosis, and management. South Med J. 2011 Nov;104(11):757-61. doi: 10.1097/SMJ.0b013e318232139f. Citation on PubMed
• Thom CS, Dickson CF, Gell DA, Weiss MJ. Hemoglobin variants: biochemical properties and clinical correlates. Cold Spring Harb Perspect Med. 2013 Mar 1;3(3):a011858. doi: 10.1101/cshperspect.a011858. Citation on PubMed or Free article on PubMed Central