In the 19th century, the remote hills of Troublesome Creek, Kentucky, were home to the Fugates, a family with a distinctive blue skin hue. This unusual coloration sparked curiosity and later led to a scientific investigation. Their striking appearance, a natural phenomenon, offered unique insight into human genetics and the impact of isolation.
The Fugate Family’s Blue Hue
The Fugate family settled in Troublesome Creek in the Appalachian Mountains in the early 1800s. Martin Fugate, an orphan from France, and his American wife, Elizabeth Smith, founded this lineage. While Elizabeth was described as pale, some accounts suggest Martin himself might have had a bluish tint.
Geographical isolation led to intermarriage within the family and with other nearby families (e.g., Smiths, Ritchies, Stacys). This contributed to the persistence of a rare genetic trait within a limited gene pool.
Affected Fugate family members had skin that was a deeper, sometimes purplish or dark blue shade. Despite their unusual appearance, many blue Fugates lived long, healthy lives, often into their 80s and 90s, with no other significant health problems directly linked to their skin color.
The Underlying Genetic Condition
The blue coloration in the Fugate family was a manifestation of a rare blood disorder called methemoglobinemia. This condition affects hemoglobin, the protein in red blood cells responsible for transporting oxygen throughout the body. Normally, the iron in hemoglobin is in a ferrous (Fe2+) state, which allows it to bind oxygen efficiently.
In methemoglobinemia, a portion of the iron in hemoglobin is oxidized to the ferric (Fe3+) state, forming methemoglobin. This altered form cannot bind and transport oxygen effectively, reducing the blood’s oxygen-carrying capacity. The accumulation of brownish-blue methemoglobin causes the skin, lips, and nails to appear bluish or purplish. The Fugates’ condition stemmed from a deficiency of the enzyme NADH-cytochrome b5 reductase (diaphorase), which converts methemoglobin back to functional hemoglobin.
Passing Down the Blue Trait
The methemoglobinemia seen in the Fugate family is inherited as an autosomal recessive trait. This means an individual must inherit two copies of the mutated gene, one from each parent, to express the condition and exhibit blue skin. Individuals inheriting only one copy are carriers; they typically show no symptoms but can pass the gene to their offspring.
The isolated Troublesome Creek community, with limited available partners, led to extensive intermarriage among relatives. This increased the probability of two carriers having children, perpetuating the rare recessive gene and the blue trait through generations. Without this geographical and social isolation, the gene would have been much less likely to manifest so prominently within the population.
Unraveling the Mystery and Treatment
In the 1960s, Dr. Madison Cawein, a hematologist from the University of Kentucky, began investigating the blue Fugates. He had heard rumors of the “blue people” and, along with nurse Ruth Pendergrass, studied the family. Cawein diagnosed their condition as a specific type of methemoglobinemia caused by the enzyme deficiency.
The treatment for this condition proved surprisingly simple and effective: methylene blue. This blue dye acts as an electron donor, helping the body’s own systems convert methemoglobin back into normal, oxygen-carrying hemoglobin. When administered, the effects were rapid, with the bluish tint fading and skin color normalizing within minutes. The Fugates’ case provided a remarkable medical discovery and enhanced understanding of rare genetic disorders and the impact of population genetics.