With a degree in biochemistry, Leah works for a small biotechnology company and enjoys writing about science.
A (Healthy) Blue Baby
"Have you ever heard of the Fugates of Troublesome Creek?"
This simple question by a knowing grandmother solved a riddle for a little boy born blue.
When little Benjamin "Benjy" Stacy was born in a small hospital near Hazard, Kentucky, he was the picture of health. He was also very, very blue. So blue, in fact, that his skin was the deep purple color of a plum. His doctors were alarmed by the sight and immediately sent him by ambulance to a hospital in Lexington, Kentucky.
Little Benjamin was subjected to an exhaustive schedule of tests in an attempt to explain the startling blue color. While he did not appear to be in any distress, doctors began to set up a blood transfusion for the tiny baby. That was when his grandmother stepped in, asking the doctors if they'd heard of the Fugates of Troublesome Creek. The boy's father, Alva Stacy, then explained that his paternal grandmother Luna was also blue—and apparently was quite healthy in life.
Benjy’s blue color started to fade a bit over the next few weeks, and as he grew, the only remaining traces of blue coloration were in his lips and nails (the color was particularly noticeable when he became cold). The doctors came to the conclusion that Benjy had inherited a rare gene found in the Appalachians—a gene that turned entire generations of one family blue.
Martin Fugate: The First Blue Man in Kentucky
In 1820, French orphan Martin Fugate and his wife Elizabeth Smith moved onto the banks of Troublesome Creek, a beautiful area in Appalachian Kentucky. There is no official record documenting that Martin was actually blue, but he and his wife both carried a recessive gene that gave their son Zachariah Fugate a startling blue color. Martin and Elizabeth had seven children—four of them were blue. Since the gene causing their blue coloration is recessive, the family had a 25% chance of having a blue child with each pregnancy if Martin and Elizabeth were carriers. If Martin was blue, the odds would have increased to 50% for each child as Martin would have carried two copies of the recessive gene.
Inbreeding was a common occurrence in the rural and isolated Appalachian region. Fugate descendants married other Fugate descendants, concentrating the “blue gene” over generations. The gene found in the Fugate family is from a line of French Huguenots, whose descendants settled in Kentucky, Ireland, and Finland.
Luna Fugate, little Benjy’s great-grandmother, was one of the bluest Fugates known to the Appalachian region. Luna was described as being blue all over, with lips the color of a dark bruise. Despite her alien-like color, she was entirely healthy and had 13 children in her 84-year span of life.
What Caused the Blue Skin Color?
The Short Answer
The blue skin was caused by a diaphorase deficiency that led to methemoglobinemia, a rare condition that causes elevated levels of methemoglobin, the form of hemoglobin that cannot bind to oxygen.
The Scientific Explanation
Scientists were quite intrigued as to the cause of the blue skin (cyanosis) in the Fugate family. In the 1960s, a young hematologist named Madison Cawein traveled to the region with the aim to cure the blue people of their skin color. The doctor hiked through the Appalachian hills on a mission to find the famous blue people of Kentucky. He finally found a couple—Patrick and Rachel Ritchie—who were willing to participate in his study.
Dr. Cawein started by ruling out any heart or lung condition that could cause the blue tint. He then suspected methemoglobinemia.
Normal Hemoglobin Function
Hemoglobin is the protein in the red blood cells that carries oxygen to other cells throughout the body. Each hemoglobin molecule is bound to four iron ions that, in turn, bind to four oxygen molecules. This process is called oxidation and converts the iron ions from their reduced form (Fe2+) to their oxidized form (Fe3+). This is also what gives blood its red color.
What Happens When Hemoglobin Is Damaged?
When hemoglobin is damaged by oxidation, the iron ions remain in their oxidized state and are unable to bind to oxygen. Normally, people have no more than 2% methemoglobin in their blood, thanks to the enzyme diaphorase—more specifically, methemoglobin reductase—that converts methemoglobin back into hemoglobin. However, in certain cases (e.g., enzyme deficiencies, inherited disorders, or exposure to toxins), methemoglobin may continue to build up over time, leading to methemoglobinemia.
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What Are the Symptoms of Methemoglobinemia?
Elevated levels aren't usually detrimental—even at 10-20% methemoglobin, when signs of slightly blue skin may be noticed. The blueness increases with increasing methemoglobin levels. At 30%, nausea, difficulty breathing, and an elevated heart rate start to appear. At 55%, people may feel extremely lethargic and go in and out of consciousness. Levels at or above 70% are considered life-threatening and are accompanied by erratic heartbeats and circulatory problems.
Absence of Diaphorase Leads to the Build-Up of Methemoglobin
The Ritchies had none of the symptoms of methemoglobinemia—nothing but their discolored skin. Working off of Dr. E. M. Scott's study of similar cases in Alaskan Eskimos and Indians—in which he found decreased levels of the enzyme diaphorase, the enzyme responsible for converting methemoglobin back to hemoglobin—Dr. Cawein performed enzyme assays on additional blood samples from other blue family members. To his amazement, he also found decreased diaphorase. The riddle was solved. This meant that methemoglobin accumulated over time, making the skin bluer and bluer.
Dr. Cawein published his research in Archives of Internal Medicine in 1964, documenting the study of this family and their congenital methemoglobinemia that was caused by a hereditary diaphorase deficiency.
An Ironic Cure for Blue Skin
To convert the blue methemoglobin back into red hemoglobin, Dr. Cawein suggested the use of a dye called methylene blue. Ironically, this blue dye could change the blue color of the affected blood into a normal red color. Vitamin C (ascorbic acid) is another method of treating the condition.
Of course, it was a tad difficult to convince the blue people of Kentucky that a blue dye would cure the condition. Nevertheless, Patrick and Rachel volunteered to try the treatment.
A simple injection of the dye caused a stunning color change. Within minutes, Patrick changed from blue to pink. This, however, was a temporary fix. The dye couldn't fix their enzyme deficiency, so Dr. Cawein left the people with a supply of methylene blue pills to be taken on a continual basis.
How Does the Methylene Blue Treatment Work?
The dye, in its reduced form, is colorless and water-soluble. When added to the blood, it acts as an electron donor, reducing the iron in the blood from Fe3+ to Fe2+ and turning blue as a result. Since it is water-soluble, it is excreted through the urine, which is why some of the older mountain people thought the blue color of their skin was literally “pouring” out of them.
As coal trains and other modern highway connectors began connecting Troublesome Creek with the rest of the nation, people began leaving the area. The gene is no longer concentrated, and the chance of intermingling between two gene carriers is remote. Still, the possibility does exist—as the parents of little Benjy Stacy proved.
What Became of Benjamin Stacy?
The little boy born blue has grown up. He attended Eastern Kentucky University, married, and lives a perfectly typical life in Fairbanks, Alaska. Other than an occasional worried comment from unknowing friends about the color of his lips or fingernails, there is little outward sign of the methemoglobinemia.
Types of Congenital Methemoglobinemia
There are several types of congenital methemoglobinemia varying in severity of symptoms. In this case, a deficiency in NADH cytochrome b5 reductase (methemoglobin reductase), a diaphorase caused members of the Fugate family to have blue skin.
Type I: This type is limited to the red blood cells and causes a blue color.
Type II: The enzyme is deficient in all tissues, and devastating systemic effects are seen—mental retardation, a small head size, and other central nervous system problems are severe. The child will also present with a blue color.
Type III: The entire blood cell system is affected, including platelets, white blood cells, and red blood cells. Fortunately, this variant does not cause any medical problems (other than a blue skin color).
Type IV: This type only affects the red blood cells and causes a chronic blue color. No other medical problems are associated with Type IV.
The majority of methemoglobinemia cases are caused by an acquired problem (e.g. the person was exposed to oxidizing drugs, toxins, or chemicals). In the case of acquired methemoglobinemia, the patient must be monitored for low blood oxygen levels and anemia since the amount of circulating normal hemoglobin may be reduced to extremely low levels.
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Questions & Answers
Question: How factual is the novel "The Book Woman of Troublesome Creek"? For example, did people actually hunt the blue people in the 1930's? I know it's possible given our historical intolerance of genetic differences, but I like to hope that at least this cruelty was fiction.
Answer: "The Book Woman of Troublesome Creek" is a work of fiction, and uses the general knowledge of the Fugate family as a base for a story of a woman who is set apart from the general community in the Appalachians. Most of the story is fictitious, including the hunting scenario. Many works of literature stray far from historical facts to generate an interesting story.
Question: When did the last blue person live?
Answer: There are people who have methemoglobinemia currently. The last member of the Fugate family to inherit the trait causing methemoglobinemia in the Appalachian mountains was Benjy Stacy, who was born in 1975. The inherited trait in this region is much less common and unlikely to be seen as the community is not as isolated as it once was.
Question: Did anyone in Mary Well's family have the blue skin trait and possibly pass it onto her which caused Martin to have blue skin?
Answer: The official family pedigree chart shows Martin Fugate (son of Benjamin Fugate and Hannah) as an individual with blue skin. The chart shows Mary Wells to be a carrier of the gene, and she was married to Martin Fugate. Mary did not display the blue skin phenotype since she only had one copy of the gene. It is unknown if anyone in Mary's family had both copies of the recessive gene. The only documented family in the area showing the blue skin phenotype due to methemoglobinemia was the Fugate family. The Smith family later intermarried the Fugate family and also carried the genes for methemoglobinemia.
There are several "Martin Fugates" in the family line, as the family pedigree starts with Josias Fugate, who married Mary Martin. Neither one of these individuals was blue. They have one documented son, named Martin, who married a woman named Sarah. Martin (the first) and Sarah were not blue, either.
Martin and Sarah have two documented children, Martin (the second) and William. Martin (the second) had blue skin and William did not. Martin the second is the first one in the family to have the phenotype. Martin the second married Mary Wells. They had three children, Hanna (likely heterozygote), James (did not carry the gene), and Zachariah (heterozygote).
At this point, Zachariah married Mary Smith, who was also a heterozygous carrier. Their son Lorenzo had both copies of the gene and had blue skin. Lorenzo married the granddaughter of Martin and Mary Wells. Zachariah and Mary Smith's other son John Fugate also displayed blue skin. After this generation, the Fugate, Smith, Ritchie, and Sevens family lines become entangled as there were several cousin marriages, increasing the number of people born with blue skin.
Question: I recall family members from earlier generations who used to talk of 'blue babies.' Is this what they could be referring to? Most of my family is in the Johnston County, NC, area but we have family sprinkled from here to the Appalachia by way of Trail of Tears descendants.
Answer: It is impossible to tell if they were referring to the isolated Fugate family in the Appalachian mountains, or if they were referring to babies who were experiencing cyanosis due to heart defects at birth. As heart defects are a fairly common condition and were not as easily treated a century ago, some "blue babies" were really suffering from a lack of oxygen due to congenital cardiac problems. The Fugate family's methemoglobinemia was isolated to their family, but it is possible your family heard tales of the "blue people in Kentucky" and shared the stories of this family.
Question: Are there blue people in Sudan?
Answer: It would be theoretically possible for a person from any region to carry the recessive genetic disorder (caused by mutations in the CYB5R3 gene). The prevalence would be low in that region. The prevalence was high within the Appalachian community because of genetic isolation. As the Appalachian community is no longer isolated, the condition is not as prevalent now.
Question: Why are these 'blue people' of Kentucky confined to one area of our country?
Answer: There are no longer "blue people" in the Appalachians. Genetic isolation is the reason this rare genetic condition was observed at a high frequency in this population. Two carriers of the rare mutation happened to meet and marry, and their offspring either had or carried the same mutations. As the area was remote and cousins married, the prevalence of the genetic variant causing methemoglobinemia increased among the family. Once the community was no longer isolated, the prevalence reduced and the disorder is no longer observed with frequency in the general area.
Question: Can a fluctuating level of diaphorase cause transient blueness? My lips turn blue, but I don't have heart problems or Sjogrens, just occasional blue lips.
Answer: Blue lips are often a symptom of poor oxygenation in general, though the cause of the poor oxygenation (and the blue lips) should be investigated by a physician. The beds of the fingernails may also turn blue due to poor oxygenation. Whether concentrations of diaphorase in your blood or another condition is causing your lips to turn blue may only be discovered via further medical testing.
Question: Is this the basis of the nursery rhyme "Little Boy Blue Come Blow Your Horn?"
Answer: This genetic condition is not the source of the nursery rhyme. The earliest reference to the Little Boy Blue nursery rhyme is in Shakespeare's King Lear play, which originally read:
"Sleepest or wakest thou, jolly shepherd?
Thy sheepe be in the corne;
And for one blast of thy minikin mouth
Thy sheepe shall take no harme"
At that time, there was no reference to the color blue. It is likely the blue was added in reference to the supposed color of the clothing the boy was wearing, not the color of his skin.
Question: Have there ever been other instances throughout history of people having methemoglobinemia?
Answer: The methemoglobinemia condition experienced in the Fugate family is rare but has been reported in other individuals. It is a recessive trait and may appear when two people who carry mutations on CYB5R3 gene (22q13.31-qter). This particular mutation causes a form of methemoglobinemia known as RCM Type 1, which results in a blue skin tone (cyanosis) at birth and has few health effects. RCM Type 1 often will cause shortness of breath on exertion. There is a second type of methemoglobinemia which is far more severe (RCM Type 2). Type 2 individuals have microcephaly and developmental delay in addition to the blue skin tone. Type 2 is caused by a total loss of NADH-cytochrome b5 reductase (Cb5R) function due to mutations on the CYB5R3 gene.
In short, there have been other instances of people who have methemoglobinemia throughout history. It is a rare condition and was more frequent in the Appalachians since the population was isolated and cousins married each other, amplifying the prevalence of the genetic mutations in that community.
Question: What caused the blue skin as experienced by the Fugate family in Kentucky?
Answer: The blue skin is caused by a condition called methemoglobinemia. Methemoglobin causes the red blood cells to carry iron in its ferric form rather than the ferrous form, which reduces the ability of the cells to carry oxygen to tissues. If the methemoglobin concentration is greater than 15%, a change in skin color and blood color are likely to be observed. In addition to the recessive trait carried by the Fugate family, other conditions may cause methemoglobinemia. The most common cause is G6PD deficiency.
Question: What is the most common hair color for the blue people?
Answer: Hair color is completely unrelated to the methemoglobinemia experienced by the Fugate family.
Leah Lefler (author) from Western New York on December 10, 2019:
Most people are skeptical when they hear about "blue people!" It is such a fascinating rare disorder. I love the fact your son is learning about such interesting topics at school, Tara. It sounds like he has a very good teacher!
Tara on December 05, 2019:
My son came home from school today telling me about the “the blue family” they was learning about it in science. I thought he was just messing around with me at first, then we looked it up. I enjoyed reading your artical and learning all about them.
Diana on October 15, 2019:
You're a great writer! What a well written and thorough article! Very informative and I learned so much more about "the blue people!" It turned into a lesson for my kids. Thanks!
Leah Lefler (author) from Western New York on September 18, 2019:
Thank you, Doug. I am glad you enjoyed the article!
Doug West from Missouri on September 18, 2019:
Leah Lefler (author) from Western New York on June 27, 2019:
The Indian god Krishna is blue in color, and the legend states he turned blue as a baby when a demon gave him poisoned milk to drink. He is also depicted as jet black in some ancient paintings. He was so attractive, enemies could not resist his charms and would always fall in love with him or give in to him. This, however, is an ancient myth and not necessarily indicative of the presence of a condition like methemoglobinemia in India. While it is possible this condition existed, there is no evidence of it at this point in time. It is fascinating to think about the various reasons for depicting an ancient god as blue in color, though, Carol!
Carol on June 19, 2019:
Ancient India had blue people. They appear in many paintings of their gods I always thought they must be aliens, but perhaps they had this meth condition of which you write above. Do you have any knowledge of the history of these people in India?
Leah Lefler (author) from Western New York on October 23, 2018:
While I can't find reports of heterozygotes displaying the blue phenotype, Janondoe, it is theoretically possible to have a situation where a carrier could display some parts of the trait. This sometimes happens in people carrying mutations for the red hair gene (compound heterozygotes may sometimes display red hair even though they don't have both copies of the same allele).
Janondoe on October 22, 2018:
Really interesting article. Do you know if one would be pre-disposed to some methemoglobin concentration with ony one copy of the gene - perhaps not enough to cause widespread turning of the skin to blue but maybe localised under some conditions?
Leah Lefler (author) from Western New York on July 13, 2018:
It is definitely an interesting genetic condition, Katharine! I love finding historical vignettes about science. I'm glad you learned something new today!
Katharine L Sparrow from Massachusetts, USA on July 13, 2018:
Very cool article! Never heard of this phenomenon. You explained it very well. This falls under the "you learn something new every day" category! Thanks!
Leah Lefler (author) from Western New York on July 04, 2018:
Thank you, Shayla!
Shayla on July 04, 2018:
I love reading great articuls hope to see more in the future
Leah Lefler (author) from Western New York on July 02, 2018:
Hypoxia caused by heart disease may also cause a blue coloration and is a more likely cause for your neighbor's coloration. The genetic condition of the Fugate family is an uncommon mutation and was more prominent when the community was genetically isolated. Methemoglobinemia does occur in different places and may definitely be the cause of tales about "blue people" in different cultures, Doris! It is fascinating to consider the various "blue people" legends around the world.
Doris James MizBejabbers from Beautiful South on June 28, 2018:
Wonderful article, Leah. Although I'm on HP, I've never seen it before. I googled "blue people" in connection with the so-called "blue people" of the early British Isles and this popped up. This is fascinating. There allegedly was a race of blue-skinned people in the Asian Pacific area back sometime in BC, but nobody seems to know where they went. I wonder if these people are descendants.
When I was a child in the Ozark mountains, a neighbor of my father's generation started turning a blue purple. Twenty years later he was totally purple. His wife told me that it was his heart that was causing it. He did die of heart disease, so I never questioned her explanation.
Leah Lefler (author) from Western New York on April 17, 2018:
The blue skin is interesting in your region, Arthur. My guess is the use of colloidal silver in the pacific northwest region - it causes permanent skin color change, even after the colloidal silver is discontinued.
Arthur on April 16, 2018:
Thank You , probably no chance of seeing him again and if i did i wouldn't approach him with Questions Leah .
Leah Lefler (author) from Western New York on April 16, 2018:
It is possible he is descended from the Fugate line, though unlikely. There are other causes for having blue skin, including the use of colloidal silver. Some people believe colloidal silver has healing properties and ingest the material, which tints their skin blue. It would be interesting to learn more about the young man you encountered, Arthur!
Arthur on April 16, 2018:
I saw and spoke very briefly to a Blue male person of about 40 years of age in the Pacific Northwest in a Grocery Store . I thought that they were concentrated in Appalachia but there he was in a small grocery store . It was interesting as i had heard about the FUGATES . He had his blonde , normal white skinned assumed son with him . Probably a FUGATE in the PNW i suppose .
Leah Lefler (author) from Western New York on March 03, 2018:
JennO, I am not sure which articles you are referring to - this is my original article and was published many years ago. I hope you can find what you are looking for!
JennO on March 02, 2018:
What happened to the longer articles/stories about the fugates? This is not the entire story... the original had many more details, and was much more interesting! No offense, but you rewrote that which was longer and more detailed.... =/
no name on February 27, 2018:
very interesting ☺
Leah Lefler (author) from Western New York on January 24, 2018:
That is a very interesting family history, Marti!
Marti on January 24, 2018:
I am a descendent of the Fugates in Troublesome who originally came from Russell County Virginia. Frances Fugate B. 1789 married William McIntosh b. 1789 my great, great great great grandfather. They have a son named Absalom, b. 1812 and married a Mulatto woman by the name of Jemima had they a daughter named Eliza. Eliza ended up marrying a black man by the name of Goeins/Goeins from Clearspring Maryland. I have traced my family all the way back to James L. Fugate born 1650 in London and Thomas Pettis from England. H was the Mayor of Norwich, Eng. Many people in Clay Co. Ky. and the Fugates and Mcintosh families had what we would call blood mixed with Native Americans and blacks as well. Some of them are in denial and never wanted to talk about the relationships between the blacks the mulatto, slaves or whatever. But black families pass the information down.
Leah Lefler (author) from Western New York on January 14, 2018:
Methemoglobin can give a gray or blue cast to the skin - it is interesting you have run across a person in Tennessee with the condition, Vickie! "Blue skin" can also be caused by colloidal silver ingestion, so some people have an acquired condition rather than genetic.
Vickie Turner on January 13, 2018:
In the summer month's my husband and I like to walk around flea markets.. One that we go to in Tenn. has a blue lady. First time I have ever seen a blue person and it's true about the color of them changing. Sometimes she's gray looking or a darker blue.
mystery on January 08, 2018:
I think this is absolutely fascinating!! I wish I could meat a blue skinned person.
phs on January 08, 2018:
this is cool and a little bit sad at the same time
Leah Lefler (author) from Western New York on December 16, 2017: