European royal families may be enormously rich, but being a blueblood doesn’t always mean your blood is pristine. Queen Victoria’s DNA is famously believed to have silently bequeathed hemophilia to many of her descendants, including a great-grandson whose severe illness played a tragic role in spurring the Russian Revolution.
And that’s not all.
There’s plenty of skepticism about this theory, which seeks to explain the “madness” of King George III. But one thing is clear. If porphyria does indeed haunt the imperial bloodline that stretches to a new generation – the late Queen Elizabeth II’s great-grandchildren – any royal who’s afflicted going forward is likely to benefit mightily from modern treatment. While this disease may require lifelong vigilance, experts said in interviews that porphyria can often be controlled.
“If patients know they have the diagnosis, and they do the right things and avoid alcohol and risky drugs, most people will have few acute attacks,” said gastroenterologist Herbert Lloyd Bonkovsky, MD, of Wake Forest University, Winston-Salem, N.C., a leading porphyria specialist.
Heme infusions can also be helpful, he added, and the revolutionary new drug givosiran is available for those who suffer recurrent attacks. And “if all else fails, a successful liver transplant is curative” – as long as the transplanted liver doesn’t have porphyria, as happened in at least one case.
But, Dr. Bonkovsky cautioned, the diagnosis is often missed, in some cases for 15 years or more.
Diagnosing porphyria: Awareness and tests are crucial
Porphyria is caused when porphyins – essential components of hemoglobin – build up in the body, disrupting systems such as the nerves, skin, and gut. The urine can turn purplish, hence the condition’s name. (Porphyrus is the Greek word for purple.)
According to hematologist Danielle Nance, MD, of Banner MD Anderson Cancer Center in Gilbert, Ariz., acute intermittent porphyria “should be suspected in persons who have recurrent severe attacks of abdominal pain requiring strong pain medication to control symptoms, and there is no obvious physical cause.”
In such cases, practitioners should send out blood and urine for porphobilinogen (PBG) and delta-aminolevulinic acid (dALA or Delta-ALA) testing, Dr. Nance said. “These are almost always elevated, even between attacks, in persons with diagnoses of acute intermittent porphyria. Other types of porphyria, such as erythropoietic porphyria, may require additional testing. Genetic testing should be offered when a patient is suspected of having porphyria, as this can speed the diagnosis.”
The typical patient is a woman from age 18 to 55, often a young woman with recurrent abdominal pain that may occur during the second half of the menstrual cycle, Wake Forest’s Dr. Bonkovsky said. Constipation is common.
“She keeps coming to the clinic or emergency department, and no one knows what’s going on. Eventually, she tends to undergo an appendectomy, often a cholecystectomy, or sometimes gynecologic procedures without cure of the disease. Only after this long and arduous road of misdiagnosis does someone think it’s porphyria and do the correct tests.”
Dr. Bonkovsky led a 2014 study of 108 subjects (81% female) with acute porphyrias and found that the average time to a correct diagnosis was a whopping 15 years. Pain in the abdomen was the most common symptom (74%), followed by nausea/vomiting (73%), weakness (63%), and constipation (60%).
While underdiagnosis is common, porphyrias can also be overdiagnosed. According to Dr. Bonkovsky, a mild increase in urinary porphyrins is often misdiagnosed as porphyria when it may be a sign of liver disease or alcohol use, instead.
Hematologist Kleber Y. Fertrin, MD, PhD, of the University of Washington, Seattle, emphasized the importance of ordering the correct tests. “Urinary porphyrins are often inappropriately ordered because of their name. They are not diagnostic for acute hepatic porphyrias and may be nonspecifically elevated. It is paramount to get the labs from a reliable lab test experienced at performing diagnostic testing for porphyrias and make sure the urine sample needed is correctly obtained and preserved.”