People From Kentucky Who Are Blue and Big Thumbs

For a hundred and fifty years, locals in the area of Hazard, Kentucky were stumped by a group of people whose skin was the color blue . The ailment, which was later revealed to be a symptom of methemoglobinemia, was contained mostly to descendants of the Fugate family of Troublesome Creek, and a related family in nearby Ball Creek. The Blue Fugates, sometimes known as the Huntsville subgroup,  were well known in the area, and their genetic disorder went unidentified until the mid twentieth century, when the amount of affected people had greatly decreased.

The Blue People of Kentucky are still discussed, but less is known about methemoglobinemia, an extremely rare genetic trait that caused the blue color of their skin. The Fugates and the met-H gene they passed for generations can teach us a valuable lesson about genetics and understanding disease.

Fugate Family: The Blue People of Kentucky

Martin Fugate, a French orphan, married a woman named Elizabeth around 1820. They settled in Troublesome Creek, Kentucky. Unbeknownst to the couple, they were coincidentally both carriers of a recessive gene (met-H) that caused methemoglobinemia, which can tint the skin of sufferers blue. Martin and Elizabeth had seven children, four of whom had blue skin. Since neither parent had symptoms of methemoglobinemia, they were shocked and confused, and no one could offer an explanation.

The area was extremely rural and isolated in the nineteenth century. There were no roads, and the railroad would not reach the area until 1910. The only other families nearby were related to Elizabeth. Due to their isolation, the Fugates began inter-marrying, which led to a higher likelihood of passing along the met-H gene, and having blue-skinned children. They became known locally as the Blue Fugates.

The Fugates' son, Zacariah, married Elizabeth's sister/his aunt. Both Zacariah and his wife were non-blue skinned carriers of the gene, and then Zacariah's children went on to marry his younger siblings and their children. Thus, the family continued passing down the trait. Unfortunately, this meant that other families in nearby communities were less likely to marry into the Fugate family for fear that they would also have blue-skinned children.

As time passed, descendants of the family moved out of the area, and new populations moved in, which allowed the Fugates to meet and marry people who did not share their genes at all. This decreased the likelihood of having children that had met-H.

Finding a Cure

In the early 1960's, two blue descendants of the family, Rachel and Patrick Ritchie, met Doctor Madison Cawein III. Cawein remembered that the two were embarrassed to be blue-skinned, since it had become associated in the area with inter-marriage. Cawein ran tests, and discovered that the levels of methemoglobin in the blood were extremely high. He determined that injections of methylene blue would be able to cure them (more later on why that worked). He injected both patients with methylene blue, and nurse Ruth Pendergrass noted that they "changed color before her eyes." Both patients continued to take methylene pills to make sure their blue color didn't return.

The last known member of the Huntsville subgroup to be born with blue skin was Benjamin Stacy in 1975. When he was born, Benjamin was so blue he was almost purple, which caused panic at the hospital. Benjamin's father remembered that the last blue Fugate before Benjamin had been his grandmother, Luna, who was a dark blue her whole life. Benjamin lost his blue coloring within a few weeks. Many Fugates were in good health despite having methemoglobinemia, and some reportedly lived into their 90's. There are no known blue-skinned Fugates today.

Understanding Methemoglobinemia

Methemoglobinemia is a blood disorder where there are elevated levels of methemoglobin in the blood. Methemoglobin is a form of hemoglobin that contains the iron Fe3. Hemoglobin is the protein in red blood cells that is responsible for transporting oxygen throughout the body, and raised levels of methemoglobin happen when the mechanisms that defend against oxidative stress are overwhelmed by Fe3. Then it converts from hemoglobin to methemoglobin. Normal methemoglobin levels are less than 1%.

Symptoms of Methemoglobinemia

People with methemoglobin levels above 10% may experience shortness of breath, headache, fatigue, dizziness, loss of consciousness, and cyanosis, the blue skin color that the Fugates were known for. Total body cyanosis, like that of the Fugates, is rare for this disorder. Typically, the blue is isolated to one part of the body.

Methemoglobin levels over 50% may result in seizures, coma, and death. Those who are otherwise healthy with levels under 15% may exhibit minor symptoms or none at all. Blood is also likely to be a chocolate brown color instead of bright red in patients with methemoglobinemia.

Genetic Causes

Met-H is a recessive gene that occurs due to an enzyme deficiency (NADH) which prohibits oxygen from traveling in the blood. With two carrier parents, a child would have a ¼ chance of being born with methemoglobinemia, a 2/4 chance of being an unaffected carrier, and a ¼ chance of not inheriting the gene at all.

This is why the Fugate family was affected so frequently. With two parents that were potentially carriers, or affected themselves, it increased the likelihood of having children who inherited the disorder or were unaffected carriers. In a diverse gene pool, a recessive trait like this one would have died out quickly, or only been a rare occurrence. The isolation made this difficult, and created a strangely perfect environment for the hereditary disorder to continue.

As the Fugates had children with people outside of the isolated Kentucky mountains that they'd originally settled, the likelihood of inheriting met-H decreased. Since it is a recessive gene, the likelihood for inheriting it becomes less likely with each generation that marries outside of the Fugate line.

Acquired Causes

Some use of antibiotics can lead to methemoglobinemia, as can use of local anesthetics and the ingestions of nitrates. Exposure to the oxidizing drugs can overwhelm the system, and convert hemoglobin into methemoglobin. It's not likely that this would be permanent, and is also unlikely to cause the "blue all over" look of the Fugates.

Infants have naturally lower levels of the enzyme NADH– the same enzyme that prohibits oxygen from traveling in the blood in those who inherit the mutation, and are at a higher risk for developing methemoglobinemia, especially when exposed to nitrates. This is sometimes called "blue baby syndrome" and those who have private water systems are at higher risk of nitrate exposure and therefore higher risk of the syndrome. This will usually go away on its own.

It can also arise in patients with kidney disease who have an impaired ability to produce NADH.

The Cure

Patrick and Rachel Ritchie, Fugate descendants, were cured by injections of methylene blue. Methylene blue restores normal iron levels in the blood by providing an artificial election receptor, which allows the NADH enzyme to work beyond its normal capacity. It's recommended that the Methylene blue is first injected slowly, and repeated if necessary. Patients then take pills for as long as they wish to continue being not-blue. Vitamin C has also been used to reduce cyanosis temporarily.

Other Blue People of Kentucky

The disorder is extremely rare. Doctor Ayalew Tefferi of the Mayo Clinic told ABC news in 2013 that "You almost never see it." Kerry Green, an Oklahoma native, has a severe version of the disease that affects his health, and his body has trouble carrying oxygen to his organs. Green cannot definitively trace his lineage back to the Fugates, but suspects he inherited the disorder from his father, whom he never met.

Another woman named Jennifer L. Adams Horsley of Indiana believed her mother-in-law had the condition as well. The family was from upper Kentucky, and Horsley claimed her mother-in-law's nails and lips were always blue, and got worse if she were cold, upset, or angry. Again, they were unable to prove a connection to the Fugates.

A man named Paul Karason famously turned blue after getting argyria, as a result of drinking colloidal silver for alleged health benefits. Karason's blue appearance and white beard drew comparisons to Papa Smurf, and brought renewed attention to the Fugate family though Karason's ailment was unrelated.

As the Fugates spread out geographically over time and generations, the disease was less likely to be passed on but also harder to track. They are not the only carriers, but certainly helped bring attention to methemoglobinemia due to the prevalence of it in their family.

The Fugates and their descendants were forced to show the world their history of inter-marriage with their blue skin. Though inter-marriage was not rare or necessarily discouraged at the time in rural Kentucky, it did lead to some unfortunate stereotypes about the people of Appalachia, a narrative the Fugates couldn't shed due to their outward appearance. Though these blue skin people were accepted socially in some places, in others they were discriminated against, pointed to as a warning against inter-marriage, and held up as a symbol of rural stereotypes.

The Fugates also showed the importance of access to medicine and medical information. Because of their family and their prominence as Blue People of Kentucky, patients today, especially blue-syndrome babies, have the benefit of information about methemoglobinemia and options for cures and treatments.

What's Next?

Looking for more information on how cells, enzymes, and genetics work? Check out this post about cell theory and why it's important and a discussion of enzymes and what they do. You can also explore how animals are biologically related to each other in Homologous and Analogous Structures: What's the Difference?

Or if you can't get enough offbeat history, check out The History of the Hole Punch and The True Story of David Ghantt and the Loomis Wells Fargo Heist.

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Carrie holds a Bachelors in Writing, Literature, and Publishing from Emerson College, and is currently pursuing an MFA. She worked in book publishing for several years, and believes that books can open up new worlds. She loves reading, the outdoors, and learning about new things.

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Source: https://blog.prepscholar.com/blue-people-of-kentucky

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