TABLE 2.

Acquired and hereditary forms of methemoglobinemia

Disease	Transmission	Cyanosis	Anemia	Other symptoms	Gene(s)	MetHb level %	CYB5R activity	Hb electrophoresis/HPLC
Drug exposure	Acquired	Yes	No	‐	‐	Variable	Normal	Normal
Methemoglobinemia, type I	Autosomal recessive	Yes since birth	No	‐	CYB5R3	20–30	Decreased	Normal
Methemoglobinemia, type II	Autosomal recessive	Yes since birth	No	Neurological involvement	CYB5R3	8–40	Decreased	Normal
Methemoglobinemia, type IV	Autosomal recessive	Yes	No	46,XY DSD Ambiguous genitalia	CYB5A	12–19	Normal	Normal
HbM disease	Autosomal dominant	Yes since birth or after HbF/A switching	Yes	‐	HBA1, HBA2, HBB, HBG1, HBG2	12–25	Normal	Abnormal
Unstable Hb	Autosomal dominant	Yes	Yes	‐	HBA1, HBA2, HBB, HBG1, HBG2	Variable (Stressor induced)	Normal	N or Abnormal

Abbreviation: DSD, disorder of sexual differentiation.