Name________________________________
NADH Dependent Methemoglobin Reductase Deficiency
(Blue People Syndrome)
NADH Dependent Methemoglobin Reductase Deficiency( Methemoglobinemia) causes
affected individuals to appear a bluish tint, particularly under conditions of stress. Like
many metabolic or enzyme deficiency disorders this is recessive. Individuals who have a
deficiency of NADH Dependent Methemoglobin Reductase Deficiency have erythrocytes(
red blood cells) which are unable to utilize glucose. Red blood cells carry hemoglobin. In the
oxygenated state hemoglobin has a reddish or pink color. In the deoxygenated state it is
dark or maroon color. In the case of methemoglobinemia, the deficiency of the enzyme
causes the change in color of the hemoglobin molecule. The disease actually results in the
malfunction of the enzyme due to a mutation in the region of the protein that forms the
active site for the enzyme. This condition occurs in Eskimos, Native Americans ( Navajo),
and an isolated populations of people near Troublesome Creek in Kentucky. This gene maps
to Chromosome 22q13.31.
Tad was the son of Jeremiah and Anna. He was born in Fairbanks, Alaska to parents of
Native American heritage. Both parents were descendents of Athebaskan Eskimos. When
he was born his skin turned gray - blue. The neonatologist in charge of the case thought
that Tad had respiratory insufficiency. After respiratory blood gas analysis, there were no
apparent problems with ventilation and breathing. X- rays, brain scans, and additional blood
tests proved inconclusive. Tad appeared to be eating, but still had a “ dusky hue”. The
doctors placed him in an oxygen tent for support. When the young resident took the family
history and drew the pedigree he was puzzled. John and Mary were Anna’s parents. Mary’s
mother was Hannah who was married to Joseph. Hannah’s sister was Zoe. Zoe was
Jeremiah’s maternal grandmother. Jeremiah’s grandfather Andrew, and his mother Alice
and father David had no sign of a blue color. Jeremiah’s sister, Sally and his brother Chad
are not married. After staring at the pedigree, the young intern believed the condition to
be hereditary. The young intern discussed the pedigree with a genetic counselor in the
hospital. After some additional tests, the doctor corroborated the basis of Tad’s condition,
a genetic disease called methemoglobinemia. In fact the entire family was shocked to find
out that Tad had inherited his blue color. Fortunately, the treatment for the disorder
prescribed was a therapeutic dose of Vitamin C. When administered to baby Tad he turned
pink like the rest of the babies in the nursery.
1.
Draw the pedigree.
2. Why didn’t any symptoms of this appear in members of Tad’s families before he was
born?
3. Do Sally and Chad have a possibility of having affected children if they marry in their
native tribe?
4. Why do rare genes appear in groups like Eskimos, Navajos, and the people of
Troublesome Creek?