Porphyria: The vampire syndrome

Brief Summary of Disease
Historically, porphyria has attracted attention as the “vampire disease”. Its symptoms include sensitivity to sunlight and discolouration of the urine. ¹ In fact, porphyrias represent a varied group of rare metabolic disorders, characterized broadly into cutaneous and acute forms. Though the exact prevalence of porphyrias is unknown, they are estimated to occur in 1-5 individuals in 10 000. Symptoms of cutaneous porphyria include blistering of the skin and oversensitivity to sunlight, whereas acute porphyria presents as neurologic attacks accompanied by severe abdominal pain. Although no cure currently exists, lifestyle changes can be made to help avoid environmental triggers. ²

“Symptoms of cutaneous porphyria include blistering of the skin and oversensitivity to sunlight, whereas acute porphyria presents as neurologic attacks accompanied by severe abdominal pain.”

Etiology & Pathology
Although symptoms can vary, a common feature in all types of porphyria is the buildup of substances called porphyrins. ² These molecules are metabolic precursors to heme, a key component of hemoglobin, the enzyme responsible for oxygen transport. The biosynthesis of heme from porphyrins involves eight enzyme-catalyzed steps. In healthy individuals, the enzymes involved in this pathway are functional. Porphyrias arise as the result of a shortage of any one of these enzymes, which leads to the accumulation of porphyrins. These molecules are harmless at low levels but can become toxic to the body in high concentrations. Porphyrias are divided into two main classes: acute and cutaneous. Acute porphyria affects the central and peripheral nervous system. Its symptoms are described as “attacks” as they appear quickly and last only a short period of time, yet can be fatal if left untreated ². Cutaneous porphyria, on the other hand, is described as a chronic illness that requires significant lifestyle changes in order to avoid the development of painful symptoms. ¹

“Porphyrias arise as the result of a shortage of any of the enzymes involved in heme biosynthesis, which leads to the accumulation of porphyrins. ”

Porphyrias display a complex inheritance pattern. Some types of porphyria are autosomal dominant, whereas other types are autosomal recessive. The inheritance of genetic forms of porphyria is an example of incomplete penetrance: not everyone who has the mutated gene will be affected. In fact, some patients have the genetic mutation but never show any signs or symptoms. ² The situation is further complicated by the fact that a complex and poorly-understood combination of environmental factors can trigger the onset of symptoms. ³ Many porphyrias are inherited, although some types are believed to be acquired solely as a result of exposure to these environmental risk factors. Risk factors include smoking, alcohol consumption, stress, fasting or dieting, and certain medications. These environmental triggers become worrisome in acute porphyria, as they can cause life-threatening attacks. ²

Symptoms
Porphyria symptoms manifest differently depending on which enzyme is deficient. In the case of acute porphyrias, symptoms most often present between the ages of 20 and 40 years. The most common form of acute porphyria is acute intermittent porphyria. During an acute porphyria attack, patients often experience muscle weakness, anxiety, vomiting, diarrhea, and abdominal pain. More severe symptoms include difficulty breathing, severe dehydration, and high blood pressure. These attacks can be life-threatening if not properly treated. Acute porphyria is far more likely to affect females than males, and it is thought that sex hormones such as progesterone may play a role in the onset of acute porphyria attacks. ⁴ Luckily, most patients with acute porphyria have only a few acute attacks in their lifetime. Some, however, have recurrent episodes every few weeks. For these patients, avoiding environmental triggers becomes critical – and potentially life-saving.

On the other hand, the severe sensitivity to sunlight associated with cutaneous forms of porphyria almost always begins in early infancy. ⁵ When exposed to the sun, the skin can become blistered, which can lead to scarring and infection. Porphyria cutanea tarda (PCT), one form of cutaneous porphyria, is classified as sporadic, meaning that it is not linked to any genetic abnormality. Unlike other forms of cutaneous porphyria, the onset of PCT occurs later in life. It is associated with photosensitivity, abnormal hair growth, and scarring of the skin. It has been linked to several conditions including hemochromatosis and hepatitis C infection but it remains unclear exactly how these conditions lead to PCT symptoms. ¹

Diagnosis
The symptoms of porphyrias are similar to those of more common diseases, rendering the disorder difficult to diagnose. ² In order to make a definitive diagnosis, laboratory tests are required, including a combination of urine, blood, and stool samples. These tests are also useful as they can classify the type of porphyria by determining which biosynthetic enzyme the patient lacks. This helps to determine which preventative steps must be taken in order to avoid exacerbation of symptoms. In the case of inherited forms of porphyria, genetic testing may be beneficial, as it can identify carriers of the disease and determine the risk of family members being affected. ⁶

“Although there is no known cure, avoiding environmental triggers can help prevent symptoms.”

Treatment
Although there is no known cure, avoiding environmental triggers can help prevent symptoms. Treatment of acute porphyria attacks involves relieving symptoms as quickly as possible and avoiding possible complications associated with these symptoms. Patients are often hospitalized to treat the dehydration and breathing problems that accompany acute attacks. ³ In some cases, a substance called hemin is administered. This molecule essentially increases heme levels in the bloodstream and slows down heme production in the body, thereby reducing porphyrin accumulation and alleviating symptoms. The main treatment method for cutaneous forms of porphyria is a reduction of exposure to sunlight. A dietary supplement for vitamin D is often prescribed to prevent a deficiency from developing. ⁵

“An important advance in the diagnosis (and potential treatment) of porphyrias is that DNA-based diagnosis is now available for every type of the disease. ”

Current Research
Other methods of treatment are also being explored. Periodic phlebotomy (withdrawal of blood) reduces iron levels in the body and decreases the production of porphyrins. A drug called hydroxychloroquine, which is used to treat malaria, can help absorb the excess porphyrins and help eliminate them from the system. An important advance in the diagnosis (and potential treatment) of porphyrias is that DNA-based diagnosis is now available for every type of the disease. A deeper understanding of the interaction between genetic and environmental factors in this complex family of disorders may allow us to uncover new methods of treatment. ⁶

Relevant Resources
The American Porphyria Foundation is an organization that aims to improve the health and wellbeing of individuals and families impacted by porphyria. Their primary goals are to support research into the prevention and treatment of the porphyrias, as well as to advocate for affected individuals and raise awareness for these disorders.

Works Cited:

1. Handler, N. S., Handler, M. Z., Stephany, M. P., Handler, G. A. & Schwartz, R. A. Porphyria cutanea tarda: an intriguing genetic disease and marker. Int. J. Dermatol. 56(2017).

2. Ramanujam, V.-M. S. & Anderson, K. E. Porphyria Diagnostics-Part 1: A Brief Overview of the Porphyrias. Curr Protoc Hum Genet 86, 17.20.1-26 (2015).

3. Gasson, T. & Klein, K. Porphyria: Pathophysiology, diagnosis, and treatment. Nurse Pract 40, 1–6 (2015).

4. Ahangari, A., Bäckström, T., Innala, E., Andersson, C. & Turkmen, S. Acute intermittent porphyria symptoms during the menstrual cycle. Internal Medicine Journal 45, 725–731 (2015).

5. Balwani, M. & Desnick, R. J. The porphyrias: advances in diagnosis and treatment. Blood 120, 4496–4504 (2012).

6. Sassa, S. Modern diagnosis and management of the porphyrias. Br. J. Haematol. 135, 281–292 (2006).

Cite This Article:

Wowk L., Chan G., Palczewski K., Zhang B., Lewis K., Ho J. Porphyria: The vampire syndrome. Illustrated by C. Tang. Rare Disease Review. November 2019. DOI:DOI: 10.13140/RG.2.2.20490.41925.