For more than a century, families living in this region called Appalachia have suffered from an extremely rare genetic blood condition that causes their skin to appear blue.
Ashamed of their green color, these families even live aloof from society, exacerbating their problems. Due to severing contact with outsiders, family members only marry cousins, aunts, and other close relatives. Therefore, the disease is inherited more widely in the family line.
According to scientists discovered in the 1960s, the mutation that causes blue skin like the cartoon character Smurf is caused by a recessive gene. Two people with the same gene will have a baby with blue skin.
Ricki Lewis, a science author who wrote the book “Human Genetics: Concepts and Applications” (roughly translated: Human Genetics: Concepts and Applications), said: “If you choose any random person, In any population of the world, maybe one in every 100,000 people will carry this gene, which is already quite high.
But if you’re married to your cousin, the odds are one in eight. The risk will skyrocket if two people are related by blood.”
Martin Fugate arrived in the desolate frontiers of Kentucky in 1820. He was a French orphan who knew nothing of his lineage. It is said that Martin’s skin itself may have had a light blue color, not dark blue like the descendants of the Fugate family later.
Martin married a red-haired American woman named Elizabeth Smith, and together the two set up a reclaimed farm on the banks of the Troublesome River near Hazard County, Kentucky. Elizabeth has pale, almost translucent skin.
What neither she nor Martin knew was that they both carried the recessive gene for a rare inherited blood disorder called methemoglobinemia.
Mr Lewis said: “This story started in a very unbelievable way because Martin moved to Kentucky from Europe and married a complete stranger, someone who was not related but happened to have the same mutation. genetic variation. This is crazy”.
According to information about the Fugate family, Martin and Elizabeth had seven children, four of whom were light blue in color.
With no rail or road links and no one else going to the Troublesome for nearly a century, the recessive blue gene was passed on to generations of the Fugates and neighboring families. All are known as “the green people of Kentucky”.
Methemoglobinemia is a blood condition, not a skin condition. It has nothing to do with melanin, the amino acid that makes human skin darker. In people with methemoglobinemia, the skin is blue because the veins underneath the skin have dark blue blood.
According to biological knowledge, blood is red because red blood cells contain a lot of protein called hemoglobin. Hemoglobin’s red color is caused by a compound called heme that contains an iron atom. That iron atom binds to oxygen, which is how red blood cells transport oxygen throughout the body.
Lack of oxygen is what causes the blood to turn from red to blue in people with methemoglobinemia. A mutated gene causes their bodies to accumulate a rare form of hemoglobin called methemoglobin that cannot bind oxygen. If enough blood is “contaminated” with this faulty type of hemoglobin, it will turn from red to a deep purple-blue.
For the Fugates, family members express genes to varying degrees. If their blood has lower levels of methemoglobin, their skin may turn blue only in cold weather, while people with higher levels of methemoglobin will have pale blue skin from head to toe.
Hypermethemoglobinemia is one of those rare genetic conditions that can be treated with a simple pill.
The man who found a cure for methemoglobinemia was Madison Cawein III, a hematologist at the University of Kentucky. He heard stories about “blue people” and went looking for samples in the 1960s.
Mr. Cawein got lucky when brothers Patrick and Rachel Ritchie entered a clinic in Hazard County. “They are strangely green,” Mr. Cawein said in an interview with Science 82 in 1982. I started asking them questions like if they had any blue relatives. Then I sat down and we started mapping their family.” He remembered that the Ritchie brothers were really embarrassed about having blue skin, but the disorder didn’t seem to cause them. any special health problems.
The condition is clearly hereditary, but the bottom line came when Mr. Cawein read reports of hereditary methemoglobinemia in segregated Inuit people living in Alaska, where blood relatives are often married. together. He knew the same thing was happening in this remote Appalachian region.
In the Inuit community, scientists have pinpointed the problem, which is a deficiency of an enzyme that converts methemoglobin into hemoglobin. Researching the problem, Mr. Cawein discovered that he could convert methemoglobin into hemoglobin without the need for enzymes. All he needed was a substance that could “donate” a free electron to methemoglobin, allowing it to bind with oxygen.
Strangely, the solution was a commonly used dye called methylene blue. He injected the Ritchie siblings with 100 milligrams of blue dye, and he didn’t have to wait long.
Mr. Cawein said: “Within minutes, the blue was gone from their skin. For the first time in their lives, they had pink skin. They are happy”.
When young people began leaving the farms around the Troublesome in the mid-20th century, they carried the recessive blue gene elsewhere. Gradually, fewer and fewer babies were born with blue skin, and those with blue skin were given blue methylene pills every day to restore their rosy cheeks.
However, there are many causes of blue skin that are not genetic. Hypermethemoglobinemia can also be caused by a reaction to some topical analgesics such as benzocaine and xylocaine. In at least one famous case, a man left his skin permanently blue by adding too much colloidal silver and applying colloidal silver cream to his skin (a condition known as argyria or silver poisoning). ).