The “Blue” People of
A Genetics Investigation
Compiled by: Matt Dean
It all started over 6 generations ago after a French orphan named Martin Fugate claimed a land grant in 1820 and settled on the banks of eastern Kentucky's Troublesome Creek, with his red-headed American bride, the former Elizabeth Smith, whose skin was as pale as the mountain laurel that blooms every spring around the creek hollows. The Fugates had seven children, four were reported to be blue. The clan kept multiplying. Fugates married other Fugates. Sometimes they married first cousins. And they married the people who lived closest to them, the Combses, Smiths, Ritchies, and Stacys. All lived in isolation from the world, bunched in log cabins up and down the hollows, and so it was only natural that a boy married the girl next door, even if she had the same last name.
"When they settled this country back then, there was no roads. It was hard to get out, so they intermarried," says Dennis Stacy who counts Fugate blood in his own veins.
Martin and Elizabeth Fugate's blue children multiplied in this natural
isolation tank. The marriage of one of their blue boys, Zachariah, to his
mother's sister triggered the line of succession that would result in the
birth, more than 100 years later of Benjy Stacy. When
Benjy was born with purple skin, his relatives told
the perplexed doctors about his great grandmother Luna Fugate. One
relative described her as "blue all over" and another calls Luna
"the bluest woman I ever saw". Luna's father, Levy Fugate, was one of
Zachariah Fugate's sons. Levy married a Ritchie girl and bought 200 acres of
rolling land along Ball Creek. The couple had 8 children, including Luna. A
fellow by the name of John Stacy spotted Luna at Sunday services of the
"They looked like anybody else, cept they had the blue color," Stacy said.
"The bluest Fugates I ever saw was Luna and
her kin," said Carrie Lee Kilburn, a nurse at the rural medical center
Luna Stacy possessed the good health common to the blue people bearing at least 13 children before she died at 84. The clinic rarely saw her and never for anything serious.
Benjy Stacy was born in a modern hospital near Hazard, Kentucky,
not far from Troublesome
Creek. He inherited his father's lankiness and his mother's red hair but
what he got from his great, great, great grandfather was dark blue skin! The
doctors were astonished, not so the parents, but the boy was rushed off to a
medical clinic in
Benjy's grandmother Stacy asked the doctor's if they had heard of the blue Fugates of Troublesome Creek. Put on that track, they concluded that Benjy's condition was inherited. Benjy lost his blue tint within a few weeks and now he is about as normal a 7-year old boy as you might imagine. His lips and fingernails still turn a purplish blue when he gets cold or angry and that trait was exploited by the medical students back when Benjy was an infant.
What causes People to Be Blue?
After ruling out heart and lung diseases, the doctor suspected methemoglobinemia, a rare hereditary blood disorder that results from excess levels of methemoglobin in the blood. Methemoglobin which is blue, is a nonfunctional form of the red hemoglobin that carries oxygen. It is the color of oxygen-depleted blood seen in the blue veins just below the skin.
If the blue people did have methemoglobinemia, the next step was to find out the cause. It can be brought on by several things: abnormal hemoglobin formation, an enzyme deficiency, and taking too much of certain drugs, including vitamin K, which is essential for blood clotting and is abundant in pork liver and vegetable oil.
Cawein drew "lots of blood" from the Ritchies and hurried back to his lab. He tested first for abnormal hemoglobin, but the results were negative.
Stumped, the doctor turned to the medical literature for a clue. He found references to methemoglobinemia dating to the turn of the century, but it wasn't until he came across E. M. Scott's 1960 report in the Journal of Clinical Investigation (vol. 39, 1960) that the answer began to emerge.
Scott was a Public Health Service doctor at the
Question 1: Genetics—The Blue People of Troublesome Creek
The year is 1975. You are a young physician working in a maternity ward near Hazard,
health in all respects except for his dark blue skin. You have lived around Hazard long
enough to remember tales about the ‘blue Fugates’ of Troublesome Creek. You wonder
if Ben is related to the Fugates, so you interview his relatives and piece together the
following genealogy. In the early 1800’s, one of Ben’s ancestors, Zacharia ‘Ball Creek
Zack’ Fugate married Mary Smith. Ball Creek Zack and Mary had 12 children, two of
whom, John ‘John Blue’, and Lorenzo ‘Blue Anze’, were blue. Ball Creek Zack’s sister,
Hannah Fugate, married James Ritchie by whom she had a normal son and daughter.
Mary’s sister, Elizabeth Smith, married Martin Fugate, a distant cousin of Ball Creek
Zack. Elizabeth and Martin had many children (7-11); none were blue. One of their
sons, Levi Fugate married Hannah and James’ daughter Mahala Ritchie. Levi and
Mahala had 8 children, 7 were normal, but their daughter Luna was blue. Luna married
John Stacy and the couple had 13 normal children. One of Luna and John’s sons (name
unknown) fathered Alva Stacey who is not blue. Alva married Hilda Gosney (also
normal) and they had Ben (born blue).
A. Complete the pedigree diagram below by putting the number of each
listed person next to the appropriate symbol.
Fugate family pedigree
1. Zacharia ‘Ball Creek Zack’ Fugate
2. Mary Smith
3. Hannah Fugate
4. James Ritchie
5. Elizabeth Smith
6. Martin Fugate
7. John ‘John Blue’ Fugate
8. Lorenzo ‘Blue Anze’ Fugate
9. Levi Fugate
10. Mahala Ritchie
11. Luna Ritchie
12. John Stacy
13. Luna and John’s son
14. Alva Stacey
15. Hilda Gosney
16. Ben Stacey
B. Color in the symbol (circle or square) for affected (blue) people.
After two days of testing, you determined that Ben Stacey’s blue skin color is
caused by methemoglobinemia. This condition results from the persistence of oxidized
iron in hemoglobin. There are several genetic disorders that lead to methemoglobinemia.
Before Alva and Hilda took Ben back home to a remote area of Hazard county, you tried
to help them understand the genetic basis for their son’s blue skin.
C. Based on the pedigree above, do you tell the Stacey’s that their son’s mutation is
1. dominant or recessive? Why?
2. X-linked or autosomal? Why?
D. Which of the listed people (please use number) must be a carrier (heterozygote)?
A few weeks after Ben Stacey returned home, his parents called to tell you that
he had lost his blue skin tone and appeared normal except that his lips and fingernails
turn blue when he is cold or angry. Family stories report that Ben’s blue ancestors were
blue throughout their lives. Over the course of the next few years, you research many
case histories of blue people and you discover that people heterozygous for mutations
that cause some forms of methomoglobinemia are blue only during their first few weeks
of life. People homozygous for the same mutations are blue throughout their lives.
E. Does this change your answer to C? If so, in what way?