Methemoglobinemia (Congenital)

At a glance

Congenital presence of high levels of methemoglobin in blood. The presence of abnormally high levels of methemoglobin in the blood is the result of a congenital anomaly of one chain of hemoglobin (hemoglobins M) or congenital deficit in NADH cytochrome b₅ reductase. Clinically, patients with a blood level around 15% present shortness of breath, cyanosis, mental status changes in 50% of patients, headache, fatigue, exercise intolerance, dizziness, and loss of hairlines. Patients with severe methemoglobinemia (>50%) have seizures, coma, and death (>70%). Healthy people may not have many symptoms with methemoglobin levels below 15%. However, patients with comorbidities, such as anemia, cardiovascular disease, lung disease, sepsis, or presence of other abnormal hemoglobin species (eg, carboxyhemoglobin, sulfhemoglobin, or sickle hemoglobin), may experience moderate-to-severe symptoms with levels as low as 5 to 8%.

Synonym

Hemoglobin M.

History

Mutations in cytochrome b₅ reductase activity were identified in 1943 by Quentin Gibson, which was considered a “Tour de Force” of clinical investigation. Gibson subsequently went on to become one of the world’s leading biochemists. History is also revealing about two groups of people affected with Met-H disorder and who received social attention in the literature. The Blue Fugates was a family located in the hills of Kentucky and affected with this medical condition. Martin Fugate settled near Hazard, Kentucky, in early 1800 and his wife was a carrier of the recessive methemoglobinemia (met-H) gene, as was a nearby clan with whom the Fugates married. This consanguineous situation led to many descendants of the Fugates that were born with met-H. The Blue Men of Lurgan, Ireland, describes two men suffering of a familial idiopathic methaemoglobinemia. The diagnosis was made by Dr James Deeny, Chief Medical Officer of the Republic of Ireland, treated these individuals in 1942 with ascorbic acid and sodium bicarbonate. Over a period of 1 month, both men regained their normal complexion.

Classification

There are two types of methemoglobinemia that consists of:

• Acquired: It is caused by medications such as antibiotics (trimethoprim, sulfonamides), local anesthetics (especially articaine, benzocaine, prilocaine) and aniline dyes, metoclopramide, rasburicase, chlorates, and bromates. Nitrates derivatives can also cause the disease. Healthy individuals are protected by normal plasmatic enzymes that rapidly reduce the methemoglobin back to hemoglobin and keep the level less than 1% at all times.

• Congenital: It is characterized by a deficit in the enzyme diaphorase I NADH-Cytochrome b₅ Reductase which allows uncontrolled increases in methemoglobin levels rise. The blood color is brown instead of red as usual.

Incidence

It is rare disorder and the exact incidence remains unknown. There are no epidemiological studies on congenital methemoglobinemia.

Genetic inheritance

Autosomal dominant (hemoglobins M), but a high rate of new mutations or ...