De novo alpha 2 hemoglobin gene (HBA2) mutation in a child with hemoglobin M Iwate and symptomatic methemoglobinemia since birth

Cyanosis in an apparently healthy newborn baby may be caused by hemoglobin variants associated with the formation of methemoglobin, collectively known as M hemoglobins. They should not be confused with genetic alterations in methemoglobin reductase enzyme systems of red cells since treatment and prognosis are completely different. A newborn male child was noted to be significantly cyanotic at birth and is the basis for this report. Hemoglobin isoelectric focusing, acid and alkaline gel electrophoresis, and HBA/HBB gene sequencing were performed for the child, both parents and a sister. The newborn child was treated with methylene blue in an intensive care unit fearing that he had a defective reductase system and exposure to oxidant drugs or toxins. Newborn hemoglobin screening with high performance liquid chromatography was abnormal on the 10th and 45th days but no conclusive diagnosis was reached. Cyanosis persisted up to four years of age with no other symptoms. Hemoglobin M Iwate [alpha2 87(F8) His>Tyr, HBA2:c.262C>T] was detected. It was not present in the child's presumed mother, father, sister, and brother. The analysis of 15 short tandem repeats in the trio demonstrated a de novo mutation occurrence (p-value < 1 × 10 -8). The family was reassured that no further action was necessary and genetic counseling was provided. Methemoglobins should be considered for differential diagnosis of cyanosis in newborns even if no familial cases are detected. Except for cosmetic consequences, the clinical course of patients with hemoglobin M Iwate is unremarkable.

Familial congenital cyanosis caused by Hb-M Yantai (alfa-76 GAC - TAC, Asp - Tyr)

Methemoglobin (Hb-M) is a rare hemoglobinopathy in China. We hereby report on a family living in Yantai, East China, with congenital cyanosis due to Hb-M mutation. The proband, a 65-year-old female, presented 63 percent oxygen saturation. Both Hb-M concentration and arterial oxygen saturation remained unchanged, even following intravenous treatment with methylene blue. There was also no change in blood-color (chocolate-brown) after adding 0.1 percent KCN. A fast-moving band (Hb-X) in hemolysates was found by cellulose acetate electrophoresis, the Hb-X/Hb-A ratio exceeding 10 percent. GT transition at 131nt of exon 2, although present in one of the alfa2-globin alleles, was not found in alfa1-globin alleles as a whole. This mutation leads to the aspartic acid to tyrosine substitution (Asp76Tyr). In this family, the novel mutation in the alfa2-globin gene resulted in a rare form of congenital cyanosis due to Hb-M. This hemoglobin was named Hb-M Yantai.

Anesthetic Implication of Hemoglobin-M: A case report / 대한마취과학회지

Cyanosis in children is most often caused by pulmonary disease, or cyanotic heart disease but is rarely caused by hematological problems such as methemoglobinemia and sulfhemoglobinemia. Abnormal hemoglobins with a reduced oxygen affinity are an exceptionally uncommon cause of cyanosis in children. Hemoglobin-M (Hb-M) is rapidly auto-oxidized into the met-form resulting in the loss of its O2-binding ability. This hemoglobinopathy is inherited in an autosomal dominant pattern and is characterized by marked cyanosis. Hb-M affects the anesthetic management because of the anomalous absorption spectrum of Hb-M in standard pulse oximetry. Sufficient O2 delivery should be maintained by keeping a high FiO2 and intermittently checking the O2 delivery state using arterial blood gas analysis. We reported our experience of the anesthetic management of a patient with hemoglobin M.