Strangely, the Kentucky clans resemble the Smurfs in having blue skin.

There are blue-skinned tribes in the remotest regions of rural Kentucky, the Fugate and Combse family being two of them. Green Combs and Green Fugate are their names.

Families in this area known as Appalachia have had this exceedingly unusual hereditary blood disorder, which turns the skin blue, for more than a century.

These family also live apart from society out of embarrassment for their green colour, which exacerbates their issues. Family members only wed their cousins, aunts, and other close relatives since they have lost contact with the outside world. As a result, the disease runs deeper in the family tree.

The mutation that results in blue skin resembling the cartoon character Smurf is thought to be produced by a recessive gene, which scientists identified in the 1960s. A kid with blue skin born from two people who have the same gene.

According to science author Ricki Lewis, who is the author of the book “Human Genetics: Concepts and Applications” (roughly translated: Human Genetics: Concepts and Applications), “If you choose any random person, There’s probably one in every 100,000 people in the world that will carry this gene, which is already quite high, but if you’re married to your cousin, it’s one in eight.” If two persons have the same lineage, the chances increase dramatically.

In 1820, Martin Fugate landed in Kentucky’s barren frontier. He was a French orphan who was unaware of his family history. According to legend, Martin’s complexion may have been a lighter shade of blue than the Fugate family’s later successors.

Elizabeth Smith, an American with red hair, and Martin established a recovered farm on the banks of the Troublesome River close to Hazard County, Kentucky. Elizabeth has pale skin that is practically transparent. She and Martin were unaware that they both possessed the recessive gene for methemoglobinemia, a rare hereditary blood condition.

“This narrative started in a really incredible way,” said Mr. Lewis, “because Martin immigrated to Kentucky from Europe and wed an unrelated stranger who also happened to share the same mutation. genetic diversity. This is absurd.

There were seven children born to Martin and Elizabeth Fugate, four of whom were light blue in colour, according to literature on the Fugate family.

Elizabeth Smith, an American with red hair, and Martin established a recovered farm on the banks of the Troublesome River close to Hazard County, Kentucky. Elizabeth has pale skin that is practically transparent. She and Martin were unaware that they both possessed the recessive gene for methemoglobinemia, a rare hereditary blood condition.

“This narrative started in a really incredible way,” said Mr. Lewis, “because Martin immigrated to Kentucky from Europe and wed an unrelated stranger who also happened to share the same mutation. genetic diversity. This is absurd.

There were seven children born to Martin and Elizabeth Fugate, four of whom were light blue in colour, according to literature on the Fugate family.

According to scientific theory, haemoglobin, a protein abundant in red blood cells, is what gives blood its red colour. The presence of an iron atom in a substance known as heme is what gives haemoglobin its red colour. Red blood cells carry oxygen throughout the body by binding that iron atom to oxygen.

Methemoglobinemia patients’ blood becomes blue instead of red due to a lack of oxygen. Their bodies build up an uncommon, oxygen-unbinding haemoglobin variant termed methemoglobin as a result of a gene mutation. The colour of the blood will change from red to a rich purple-blue if enough of this defective kind of haemoglobin is “contaminated” in it.

For the Fugates, different family members express genes differently. People with greater amounts of methemoglobin will have light blue skin from head to toe, whereas those with lower levels of methemoglobin may only have occasional bouts of blue skin in cold weather.

One of the uncommon hereditary diseases that may be addressed with a single medication is hypermethemoglobinemia.

Madison Cawein III, a haematologist at the University of Kentucky, was the person responsible for discovering a treatment for methemoglobinemia. In the 1960s, he became interested in “blue people” after hearing tales about them.

When brothers Patrick and Rachel Ritchie walked into a clinic in Hazard County, Mr. Cawein struck lucky. Mr. Cawein commented, “They are strangely green,” in an interview with Science 82 from 1982. I began questioning them, such as whether they were related to any blue people. I sat down after that, and we began charting their family. He recalled that the Ritchie brothers were quite ashamed of their blue skin, despite the fact that the disease didn’t seem to be the reason. any unique health issues.

Although Mr. Cawein read tales of hereditary methemoglobinemia in separated Inuit people living in Alaska, where blood relatives are frequently related, the conclusion that the ailment is genetic became evident to him that what really mattered. They exchange kisses. He was aware that the same thing was taking on in this isolated Appalachian area.

Scientists have identified the issue in the Inuit population as a lack of an enzyme that transforms methemoglobin into haemoglobin. Mr. Cawein investigated the issue and found a way to produce haemoglobin without the need of any enzymes. To get methemoglobin to bond with oxygen, all he need was a chemical that could “donate” a free electron to it.

Strangely, methylene blue, a popular dye, was the remedy. He injected 100 milligrammes of blue dye into the Ritchie siblings, and he didn’t have to wait long.

The blue vanished from their skin in a matter of minutes, according to Mr. Cawein. They had pink skin for the first time in their lives. They are content.

In the middle of the 20th century, as young people started moving away from the farms near the Troublesome, they took the recessive blue gene with them. The number of newborns with blue skin decreased over time, and those who did received daily tablets containing blue methylene to restore their red cheeks.

There are several non-genetic reasons of blue skin, though. A negative reaction to several topical analgesics, such as benzocaine and xylocaine, can also result in hypermethemoglobinemia. By mixing too much colloidal silver and applying it topically to his skin (a disease known as argyria or silver poisoning), a man at least once famously turned his skin permanently blue.