Regular removal of blood, through a procedure called phlebotomy, reduced symptoms and porphyrin levels in a person with congenital erythropoietic porphyria (CEP), likely by reducing iron levels in the body, according to recent case report that recommends targeting iron levels as a strategy to manage the disease.
The case report, titled “Phlebotomy As An Efficient Long-Term Treatment Of Congenital Erythropoietic Porphyria,” was published in Haematologica.
CEP is caused by mutations that ultimately impair the function of the protein uroporphyrinogen III synthase, which is necessary for making hemoglobin — the molecule used to ferry oxygen in the blood. This leads to the accumulation of porphyrin in blood cells and causes the symptoms of CEP, such as photosensitivity or sun allergy.
In a previous report, an individual with CEP experienced a marked improvement in photosensitivity and other symptoms after bleeding events led to iron deficiency. This effect was maintained with the use of an iron chelator (a drug that removes iron from the body).
This finding suggested that reducing iron levels could be an effective treatment strategy for CEP. The benefit is presumed to be due to decreased activity of other proteins that act in the same pathway as uroporphyrinogen III synthase, ultimately leading to less porphyrin being made and accumulating.
However, accomplishing this effect with an iron chelator may not be the most feasible strategy.
“The use of an iron chelator is a suitable treatment under iron overload, but its benefit and toxicity have not been evaluated in normal and iron-deficient states,” the new case report stated. The researchers further noted that long-term use of iron chelators is associated with toxicity to multiple organs, such as the liver and kidneys, limiting their regular use.
A different method to feasibly remove iron from the body would be to remove blood, as a great deal of the body’s iron is stored in blood. The removal of blood is called a phlebotomy; this is the same procedure done when blood is collected for laboratory testing.
The patient described in the case report was a 49-year-old white female who began experiencing the symptoms of CEP at age four and was diagnosed at 25.
Her condition was treated with regular phlebotomies over nearly two years — initially to remove 100 mL of blood twice a month, which was increased to 300 mL over the next eight months.
During this time, the patient experienced less photosensitivity and had clearer urine (dark urine is a common porphyria symptom). In addition, levels of porphyrin decreased by 79% in the urine and by 85% in the blood.
The phlebotomy treatment was then stopped for three months, at which point her porphyrin levels increased and photosensitivity worsened. Phlebotomies were then reintroduced on a monthly schedule, removing increasing amounts up to 300 mL for the next seven months, then removing 200 mL per month.
After a total of 23 months (the last recorded data point), the patient’s symptoms had again improved, and porphyrin levels had decreased by 83% in the urine and 91% in the blood, compared to initial values.
“The biological and clinical improvement allowed the patient to have unrestricted solar exposure during summer without showing any signs of blistering,” the researchers wrote.
Additionally, no serious adverse events were reported, though the patient did experience some lethargy and weakness.
“We can thus propose phlebotomies as a simple, universally available, well-tolerated and inexpensive strategy for treating CEP,” the researchers wrote.
More broadly, this finding supports the modulation of iron levels as a therapeutic strategy for CEP. Further research will be needed to fully understand the mechanism behind this phenomenon, the researchers said.
Their report also briefly described a family in which three biological siblings were affected by CEP, but one sibling, who had a severe iron deficiency, had much lower porphyrin levels and less severe symptoms. While this finding alone doesn’t indicate a cause-and-effect relationship between iron levels and CEP, it further adds to the data suggesting such a link.
“[T]he observation of siblings with contrasting phenotypes modulated by iron availability highlights the importance of iron regulation in CEP,” the researchers wrote.