OBSOLETE: Recessive hereditary methemoglobinemia type 2

Recessive hereditary methemoglobinemia type 2 (also known as cytochrome b5 reductase deficiency type II, or NADH-cytochrome b5 reductase deficiency type II) is a severe form of congenital methemoglobinemia caused by a generalized deficiency of the enzyme cytochrome b5 reductase (CYB5R3) in all cell types. This Orphanet entry (139380) is marked as OBSOLETE, meaning it has been reclassified or merged into another entry in current nosology. The condition was historically distinguished from type 1 (which affects only red blood cells) by its systemic involvement, leading to severe neurological impairment in addition to cyanosis. In this condition, the enzyme deficiency prevents the normal reduction of methemoglobin back to functional hemoglobin in red blood cells, resulting in persistent cyanosis (bluish discoloration of the skin and mucous membranes) from birth. More critically, the generalized enzyme deficiency affects the brain and nervous system, causing progressive neurological deterioration including intellectual disability, microcephaly, opisthotonus, movement disorders, and failure to thrive. Onset is typically in the neonatal or early infantile period. Most affected individuals have a significantly shortened lifespan. Treatment options are limited. While methylene blue and ascorbic acid can partially reduce methemoglobin levels and improve cyanosis, these treatments do not address the underlying neurological damage. Supportive care and management of neurological symptoms remain the mainstay of treatment. There is currently no curative therapy available. Patients and families seeking current classification should refer to the updated Orphanet entry for recessive hereditary methemoglobinemia type 2, as this specific code is no longer in active use.

Common questions about OBSOLETE: Recessive hereditary methemoglobinemia type 2