The “Blue” People of Kentucky

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 Old Regular Baptist Church before the turn of the century. Stacy courted her,
married her, and moved from Troublesome Creek to make a living in timber on her
daddy's land. John Stacy still lives on Lick Branch of Ball Creek. Stacy recalls that his
father-in-law, Levy Fugate, was "part of the family that showed blue. All them old
fellers way back then was blue. One of em - I remember seeing him when I was just a
boy - Blue Anze, they called him. Most of them old people we knew by that name -
the blue Fugates. It run in that generation who lived up and down Ball Creek".

"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 called Homeplace Center. "Luna was bluish all over.
Her lips were as dark as a bruise. She was as blue a woman as I ever saw."

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 Lexington (University of Kentucky Medical School). Two days of tests
showed no cause for Benjy's blue skin.

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 Arctic Health Research Center in Anchorage who had discovered
hereditary methemoglobinemia among Alaskan Eskimos and Indians. It was caused,
Scott speculated, by an absence of the enzyme diaphorase from their red blood cells.
In normal people hemoglobin is converted to methemoglobin at a very slow rate. If
this conversion continued, all the body's hemoglobin would eventually be rendered
useless. Normally diaphorase converts methemoglobin back to
hemoglobin. Cawein was eventually able to determine that this same disorder, the lack
of the diaphorase enzyme, affected the Blue Fugates.

Questions

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, Kentucky. One night, you are called to attend a newborn boy, Ben Stacy, who
is in good 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?