OBSOLETE: Recessive hereditary methemoglobinemia type 1

Recessive hereditary methemoglobinemia type 1 (also known as congenital methemoglobinemia type 1, or NADH-cytochrome b5 reductase deficiency type 1) is an inherited condition in which the blood contains elevated levels of methemoglobin — a form of hemoglobin that cannot effectively carry oxygen to the body's tissues. This Orphanet entry (ORPHA:139373) is classified as OBSOLETE, meaning it has been retired and its clinical content has been merged into or replaced by other active disease entries in the Orphanet classification. Patients and clinicians seeking information about this condition should refer to the current Orphanet entry for recessive congenital methemoglobinemia type 1 (ORPHA:521) or the broader category of hereditary methemoglobinemia. In the active form of this disease, affected individuals typically present with cyanosis (a bluish discoloration of the skin, lips, and nail beds) from birth or early infancy due to the impaired oxygen-carrying capacity of their blood. The condition is caused by pathogenic variants in the CYB5R3 gene, which encodes cytochrome b5 reductase 3, the enzyme responsible for reducing methemoglobin back to functional hemoglobin. Type 1 is the milder, erythrocyte-restricted form, primarily affecting red blood cells without involvement of the nervous system. Most individuals with type 1 are otherwise healthy, though they may experience headaches, fatigue, and exercise intolerance in addition to persistent cyanosis. Treatment for the underlying condition includes oral methylene blue or ascorbic acid (vitamin C), which can help reduce methemoglobin levels and improve cyanosis. Riboflavin has also been used as a supplementary treatment. The prognosis for type 1 is generally favorable, with a normal life expectancy. Because this specific Orphanet code is obsolete, patients should consult updated resources for the most current clinical guidance.

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