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April 2001, Vol. 4
No. 4, p. 80.
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Diseases and Disorders
JULIE L. MCDOWELL

Painful porphyrins


“I was only 17 years old when I suffered my first attack of porphyria. The onslaught of pain was rapid and vicious. When I was asked by the attending physician to describe the pain, I likened the agony to that caused by a thousand flaming swords embedded deeply in my abdomen.”

Painting of George III of Britain
From 1760 to 1820, George III of Britain suffered four major “madness” episodes. Researchers have speculated that porphyria was the cause.

Heme is synthesized from smaller molecules through a sequence of enzymatic steps.
Heme is synthesized from smaller molecules through a sequence of enzymatic steps. An enzyme deficiency at any point causes porphyrin accumulation.
Desiree Lyon, executive director of the American Porphyria Foundation for the past 19 years, recovered from this initial attack of severe abdominal pain without a diagnosis. Her physicians could not explain her condition, and they concluded that she had a low pain threshold for menstrual cramping.

Five years later, the “pain reappeared with a vengeance,” according to Lyon. For 15 years, she was in and out of intensive care. Besides the severe pain, she experienced various other physical symptoms that came and went cyclically—extreme weakness, labored breathing, minor seizures, and purplish urine. Physicians still failed to find a cause for her illness.

It was not until a chance meeting with an acquaintance at a party that Lyon started to discover what was making her ill. When George Penton, a physician friend, noted her gray pallor and general ill disposition, Lyon briefly related her symptoms and her medical history of tests and misdiagnoses. Penton promised that he would determine her condition, but she would have to endure additional tests.

After a series of tests showed no conclusive results, Penton prescribed Dilantin, a medication for Lyon’s small seizures. Within hours of taking the medicine, Lyon was paralyzed with pain and suffering from hallucinations; she lost her ability to speak—only garbled babble was coming out of her mouth. She was immediately admitted into intensive care, where her organs began shutting down. Dr. Penton prepared her family for her death.

After a catheter was inserted during the initial hours in intensive care, Penton noticed that Lyon’s urine bag filled with what appeared to be dark blood. A urinalysis showed that her deep-red-colored urine was caused by a high accumulation of porphyrins. Penton suspected that Lyon had porphyria, a genetic disease he had studied in medical school but had never seen in a patient.

Porphyrins are complex molecules in the body that combine with iron to produce heme, which is responsible for giving blood its red color and combines with globin to form hemoglobin. Besides delivering oxygen through the body’s circulatory system, heme is important in metabolism and human physiology.

Porphyria is a genetic disease that is caused by an enzyme deficiency in heme production. Heme is synthesized from smaller molecules through several enzyme-catalyzed steps in a biochemical pathway. An enzyme deficiency in any of these steps inhibits heme production, causing porphyrins to accumulate and clog the pathway. The high level of porphyrins is responsible for the physical symptoms, such as port-colored urine, sensitivity to sunlight, and the mental instability that sometimes accompanies this disease. Attacks occur when porphyrins become elevated, depending on the patient’s tolerance. Alcohol, smoking, or prescription drugs that cause the body to respond by accumulating porphyrins can precipitate attacks.

Penton knew that there was no cure for porphyria, because its root cause is a defective gene. He placed Lyon on hematin, which is chemically synthesized heme from human or animal blood. Lyon quickly felt relief from the constant pain, but she did not recover from the extreme weakness for many months.

Several laboratories are investigating the mysteries surrounding porphyria. For example, Nicholas Jacobs, a retired professor from Dartmouth Medical School, conducted research in 1999 to see whether various enzymes, in conjunction with dietary components, could detoxify porphyrins. His results were promising, but Jacobs stresses that the tests were performed in test tubes, not humans. Jacobs is optimistic about these results, but he thinks that gene therapy will prove successful in conquering porphyria. Lyon agrees with him, adding, “The future lies in genetic treatment, including enzyme replacement and gene therapy.”

For more information:

For a full account of Desiree Lyon’s illness, visit the American Porphyria Foundation at www.enterprise.net/.

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