  methemoglobinemia (or methaemoglobinaemia) is a disorder characterized by the presence of a higher than normal level of methemoglobin (methb, i.e., ferric [fe3+] rather than ferrous [fe2+] haemoglobin) in the blood. methemoglobin is a form of hemoglobin that contains ferric [fe3+] iron and has a decreased ability to bind oxygen. however, the ferric iron has an increased affinity for bound oxygen. the binding of oxygen to methemoglobin results in an increased affinity of oxygen to the three other heme sites (that are still ferrous) within the same tetrameric hemoglobin unit. this leads to an overall reduced ability of the red blood cell to release oxygen to tissues, with the associated oxygenâhemoglobin dissociation curve therefore shifted to the left. when methemoglobin concentration is elevated in red blood cells, tissue hypoxia can occur.  ==pathophysiology== normally, methemoglobin levels are <1%, as measured by the co-oximetry test. elevated levels of methemoglobin in the blood are caused when the mechanisms that defend against oxidative stress within the red blood cell are overwhelmed and the oxygen carrying ferrous ion (fe2+) of the heme group of the hemoglobin molecule is oxidized to the ferric state (fe3+). this converts hemoglobin to methemoglobin, resulting in a reduced ability to release oxygen to tissues and thereby hypoxia. this can give the blood a bluish or chocolate-brown color. spontaneously formed methemoglobin is normally reduced (regenerating normal hemoglobin) by protective enzyme systems, e.g., nadh methemoglobin reductase (cytochrome-b5 reductase) (major pathway), nadph methemoglobin reductase (minor pathway) and to a lesser extent the ascorbic acid and glutathione enzyme systems. disruptions with these enzyme systems lead to methemoglobinemia. hypoxia occurs due to the decreased oxygen-binding capacity of methemoglobin, as well as the increased oxygen-binding affinity of other subunits in the same hemoglobin molecule which prevents them from releasing oxygen at normal tissue oxygen levels. ==clinical signs and symptoms== signs and symptoms of methemoglobinemia (methemoglobin >1%) include shortness of breath, cyanosis, mental status changes (~50%), headache, fatigue, exercise intolerance, dizziness and loss of consciousness. patients with severe methemoglobinemia (methemoglobin >50%) may 
Autosomal_recessive_disorders Red_blood_cell_disorders