VIDEO: The Blue Skinned People of Kentucky

The Fugates, a family that lived in the hills of Kentucky, are notable for having been carriers of a genetic trait that led to the disease methemoglobinemia.

The condition gives sufferers blue-tinged skin.

According to Wikipedia, French-born Martin Fugate, orphaned as a child, settled near Hazard, Kentucky, circa 1820. Because of the remote rural area in which they and other nearby families had settled, there was a very high level of consanguinity in marriage between families.

His wife Elizabeth Smith was a carrier of the recessive methemoglobinemia (met-H) allele, as was a nearby clan with whom the Fugates intermarried. As a result, many descendants of the Fugates were born with met-H.

Descendents with the disease gene continued to live in the areas around Troublesome Creek and Ball Creek into the 20th century, eventually coming to the attention of the nurse Ruth Pendergrass and the hematologist Madison Cawein III, who made a detailed study of their condition and ancestry.

Cawein treated the family with methylene blue, which eased their symptoms and reduced the blue coloring of their skin. He eventually published his research in the Archives of Internal Medicine in 1964.

As travel became easier in the 20th century, and families spread out over wider areas, the prevalence of the recessive gene in the local population reduced, and with it the probability of inheriting the disease.

Benjamin Stacy, born in 1975, is the last known descendent of the Fugates to have been born exhibiting the characteristic blue color of the disease, and lost his blue skin tone as he grew older.

It has been speculated that some other American sufferers of inherited methemoglobinemia may also have had Fugate ancestors, but searches for direct links have so far proved inconclusive.

Methemoglobinemia is a condition caused by elevated levels of methemoglobin in the blood. Methemoglobin is a form of hemoglobin that contains the ferric form of iron. The affinity for oxygen of ferric iron is impaired.

The binding of oxygen to methemoglobin results in an increased affinity for oxygen in the remaining heme sites that are in ferrous state within the same tetrameric hemoglobin unit.

This leads to an overall reduced ability of the red blood cell to release oxygen to tissues, with the associated oxygen–hemoglobin dissociation curve therefore shifted to the left. When methemoglobin concentration is elevated in red blood cells, tissue hypoxia may occur.

Signs and symptoms of methemoglobinemia (methemoglobin level above 1%) include shortness of breath, cyanosis, mental status changes (~50%), headache, fatigue, exercise intolerance, dizziness and loss of hairlines.

Patients with severe methemoglobinemia (methemoglobin level above 50%) may exhibit seizures, coma and death (>70%). Healthy people may not have many symptoms with methemoglobin levels below 15%.

However, patients with co-morbidities such as anemia, cardiovascular disease, lung disease, sepsis, or presence of other abnormal hemoglobin species (e.g. carboxyhemoglobin, sulfhemoglobin or sickle hemoglobin) may experience moderate to severe symptoms at much lower levels (as low as 5–8%).

Arterial blood with elevated methemoglobin levels has a characteristic chocolate-brown color as compared to normal bright red oxygen-containing arterial blood. If methemoglobinemia is suspected, an arterial blood gas and co-oximetry panel should be obtained.