ORPHA: 330041;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 11p15.4 | Methemoglobinemia, beta type | 617971 | Autosomal dominant | 3 | HBB | 141900 |
A number sign (#) is used with this entry because this form of methemoglobinemia is caused by heterozygous mutation in the beta-globin gene (HBB; 141900) that produces M hemoglobin, a methemoglobin not amenable to reduction, or a hemoglobin with an unusual susceptibility to oxidizing agents.
Methemoglobinemia is a clinical condition in which more than 1% of hemoglobin is oxidized to methemoglobin, a type of hemoglobin that contains the ferric (Fe3+) form of iron. Patients with hemoglobin M are cyanotic but otherwise asymptomatic. If the mutation occurs in the hemoglobin alpha subunit (141800), cyanosis is apparent at birth, whereas if the beta chain is affected, cyanosis appears later or intensifies when beta subunit production increases. If a newborn carries a fetal M hemoglobin (gamma subunit; 142250), cyanosis disappears when the complete gamma-beta-switch occurs (summary by Mansouri and Lurie, 1993).
Gerald and Efron (1961) reviewed 5 different M hemoglobins, all of which caused chronic cyanosis due to the occurrence of methemoglobinemia.
Methemoglobinemia caused by mutation in the beta-globin gene is inherited in an autosomal dominant manner.
Hayashi et al. (1969) noted that 4 M hemoglobins, Hb M (Iwate) (141800.0093), Hb M (Hyde Park) (141900.0164), Hb M (Boston) (114800.0092), and Hb M (Saskatoon) (141900.0165), have a structural abnormality in the proximal or the distal histidine of the alpha or beta subunits of the Hb molecule and have the same kind of amino acid substitution, histidine to tyrosine. These 4 amino acids are critical to the binding of the heme group. A fifth variant of Hb M, Hb M (Milwaukee-1) (141900.0165), has a valine to glutamic acid substitution at a position 4 residues or one helical turn from the distal histidine. Mansouri and Lurie (1993) noted that in this Hb variant, the carboxylic group of the glutamic acid forms a bond with iron, thus stabilizing it in the oxidized form.
Gerald, P. S., Efron, M. L. Chemical studies of several varieties of Hb M. Proc. Nat. Acad. Sci. 47: 1758-1767, 1961. [PubMed: 13897827] [Full Text: https://doi.org/10.1073/pnas.47.11.1758]
Hayashi, A., Suzuki, T., Imai, K., Morimoto, H., Watari, H. Properties of hemoglobin M, Milwaukee-1 variant and its unique characteristic. Biochim. Biophys. Acta 194: 6-15, 1969. [PubMed: 4311041] [Full Text: https://doi.org/10.1016/0005-2795(69)90173-1]
Mansouri, A., Lurie, A. A. Methemoglobinemia. Am. J. Hemat. 42: 7-12, 1993. [PubMed: 8416301] [Full Text: https://doi.org/10.1002/ajh.2830420104]