Hemoglobin M disease

Hemoglobin M disease
Bluish fingertips in a cyanotic patient
Symptoms	Cyanosis and dark brown blood
Causes	Hemoglobin M variants
Diagnostic method	Hemoglobin electrophoresis, UV spectroscopy, DNA sequencing, etc.
Treatment	No treatment is required

Hemoglobin M disease is a rare form of hemoglobinopathy, characterized by the presence of hemoglobin M (HbM) and elevated methemoglobin (metHb) level in blood.^[1] HbM is an altered form of hemoglobin (Hb) due to point mutation occurring in globin-encoding genes, mostly involving tyrosine substitution for proximal (F8) or distal (E7) histidine residues.^[2] HbM variants are inherited as autosomal dominant disorders and have altered oxygen affinity.^[3] The pathophysiology of hemoglobin M disease involves heme iron autoxidation promoted by heme pocket structural alteration.^[4]

There exists at least 13 HbM variants, such as Boston, Osaka, Saskatoon, etc., named according to their geographical locations of discovery. Different HbM variants may give different signs and symptoms. Major signs include cyanosis and dark brown blood. Patients may be asymptomatic or experience dizziness, headache, mild dyspnea, etc.^[2][5] Diagnosis is usually suspected based on cyanosis. Biochemical testing, hemoglobin electrophoresis, ultraviolet-visible wavelength light spectroscopy, and DNA-based globin gene analysis can be used for diagnosis.^{[2][5][6][7][8][9][10]} Hemoglobin M disease is often not life-threatening and there is no known effective treatment.^{[3][5][10][11][12][13]}

Hemoglobin M disease is a congenital subtype of methemoglobinemia.^[2] For other congenital subtypes of methemoglobinemia, cytochrome b5 reductase (CYB5R) deficiency is the major cause, rendering defective conversion of metHb to normal Hb. CYB5R deficiency is an autosomal recessive condition.^[14]