What is Acute Porphyria?
Acute porphyria is a term that describes a set of uncommon diseases caused by an enzyme malfunction in the process that makes heme, a crucial component of the body. The disorders may lead to severe, potentially life-threatening episodes triggered by factors such as certain medicines, hormonal changes, or even lack of food. This article will discuss the symptoms, how it is diagnosed, and how acute porphyria is managed.
What Causes Acute Porphyria?
Acute porphyrias are conditions that are inherited or passed down through families. However, the presence of certain environmental or physical factors like drugs is necessary for symptoms to appear. Porphyria is essentially a disorder that you get from your genes. Now, how the genes express themselves, or show symptoms, can vary. It’s found more often in people who have family members with the condition.
Two percent of the general population is found to have a 50% dip in the activity of aminolevulinic acid dehydratase, an enzyme linked to porphyria, although, symptoms usually only occur when there’s over a 90% decrease in the enzyme activity.
Till date, over 100 mutations connected to porphyria have been found. The symptoms usually correspond with a 50% or greater decrease in enzyme function. An enzyme called porphobilinogen deaminase could have three different types of mutations:
* Type 1: A wrong single unit causes a replacement of an amino acid
* Type 2: Only happens in the enzyme’s tissue variant
* Type 3: Missing sections in parts of the enzyme called exons
Hereditary coproporphyria, a type of porphyria, is caused by a wide variation and abnormal function of an enzyme called coproporphyrinogen oxidase. This variation makes it quite difficult to conduct routine genetic tests. People carrying one or both copies of the gene mutation show a 50% and 90-98% reduction in the enzyme, respectively.
In all the tests conducted, a 50% reduction in an enzyme called protoporphyrinogen oxidase was found. Mental delay is a common symptom in newborns with variegate porphyria, another type of porphyria.
Risk Factors and Frequency for Acute Porphyria
Autosomal dominant acute porphyrias are conditions that equally affect men and women. These conditions are found in all racial and ethnic groups worldwide. However, some populations have a higher prevalence due to the founder effect. This means that certain groups have a higher number of cases because of their shared genetics. For instance, the Afrikaner population in South Africa, who are original settlers from the Netherlands, have a high number of cases of variegate porphyria (VP). Similarly, northern Scandinavian populations have more cases of acute intermittent porphyria (AIP) than average.
- Autosomal dominant acute porphyrias can affect any ethnic or racial group equally.
- Acute porphyrias are more common in the Afrikaner population of South Africa and northern Scandinavian populations. This increased prevalence is due to shared genetic factors among these specific groups.
- The prevalence of AIP is about 5-10 cases per 100,000 people.
- Acute porphyrias are generally more common in women, likely due to the influence of female sex hormones.
- While most patients begin to show symptoms after puberty, the disease can manifest in childhood as well.
Signs and Symptoms of Acute Porphyria
Acute porphyria often first appears in teenagers or young adults. It’s common for women to have symptoms beginning with their menstrual cycle. The most recognizable symptoms of an acute attack include severe belly pain, nausea, constipation, rapid heart rate, high blood pressure, and various symptoms related to the nervous system like seizures, temporary paralysis, and confusion. There can also be psychiatric disturbances during an episode, with changes in behavior, agitation, depression, hallucinations, and altered mental status occurring in up to 80% of cases. Patients often report the darkening of their urine during an attack. And even though not exclusively related to this condition, stomach pain is the most common reason these patients are hospitalized.
During a medical visit, the doctor will ask detailed questions about the patient’s recent use of medications, alcohol consumption, family history of porphyrias, use of hormonal therapy, and women’s menstrual cycle history. This information is crucial because certain triggers can spark an acute porphyria attack. It’s also worth noting that there are online resources providing safety information about the use of different drugs in relation to porphyria, one of them being www.porphyriafoundation.com/drugs.
Upon physical examination, a patient might have high blood pressure, increased heart rate, show signs of irregular heart rhythm, weakened muscle strength, or have difficulty breathing. There also may be signs of damage to the nerves outside the brain and spinal cord. Skin problems, such as blisters and sores on the skin that’s exposed to the sun, may also be a sign of the condition, particularly in cases of certain specific types of acute porphyrias.
- Severe belly pain
- Nausea
- Constipation
- Rapid Heart Rate
- High Blood Pressure
- Nervous system symptoms (e.g., seizures, temporary paralysis, confusion)
- Psychiatric disturbances (e.g., change in behavior, agitation, depression, hallucinations)
- Darkening of the urine
- History of hormonal therapy
- Menstrual history in females
- Recent alcohol consumption
- Heart rhythm irregularities
- Weakened muscle strength
- Difficulty breathing
- Signs of nerve damage
- Skin blisters and sores in sun-exposed areas
Testing for Acute Porphyria
Acute porphyria often overlaps with many other conditions, so making a diagnosis can be challenging. Symptoms often include abdominal pain, neurological issues, and mental disturbances. If these symptoms are present, a suspicion of acute porphyria should be considered.
Generally, the main way to identify acute porphyria is through biochemical testing. This includes checking the levels of heme precursors and porphyrins – unique compounds involved in producing heme, a part of our blood – in urine, feces, or blood. These levels are usually elevated during a flare-up of porphyria but can be normal when the disease is inactive or in people who aren’t symptomatic. Different porphyrins dissolve differently, so you might find some more in urine and others in feces.
During an episode, some general lab tests might show low sodium levels or higher-than-normal levels of urea, creatinine, and transaminases due to dehydration or kidney problems. However, the white blood cell count is usually normal unless there’s another infection present.
Acute porphyria is characterized by an increase in a molecule called porphobilinogen (PBG) in the urine; this increase can be about ten times the normal amount. Testing random urine samples can help detect this. The Watson-Schwartz test can provide an immediate assessment right at a bedside to check for PBG in the urine. Quantitative methods can also be used to precisely measure the PBG levels. However, it’s important to note that even individuals who carry genes for porphyria but show no symptoms may have higher PBG levels.
Once acute porphyria is diagnosed, the next step involves figuring out which type it is. Techniques like high-performance liquid chromatography can help identify different types of porphyrins in urine. Additional tests like fecal porphyrin analysis can also assist in distinguishing different kinds of acute porphyria.
All samples used for testing porphyria — urine, feces, or plasma — must be shielded from light during collection and transport to maintain their accuracy.
Finally, genetic testing can also be useful. It can both confirm a diagnosis in a patient and also help ascertain if other family members might be at risk. However, not finding a genetic mutation does not definitively rule out the possibility of acute porphyria. As always, genetic counseling should be provided along with tests of this kind.
Treatment Options for Acute Porphyria
When dealing with an acute attack of porphyria, the first step is typically to address any factors that could have caused the attack. This might include stopping any medications that might have induced the attack, rehydrating the patient with IV fluids such as normal saline and glucose, and managing any pain that may be present. This pain can be safely treated with opioids.
The gold standard for treating an acute attack of porphyria is an IV treatment with hemin, which needs to be given for approximately 3-14 days. Hemin counteracts the increase in ALAS1, an enzyme that is elevated during a porphyria attack. Researchers are also investigating the use of small interfering RNA (siRNA) to ALAS1, and one specific drug, Givosiran, has been approved for managing acute hepatic porphyrias in adults.
There’s currently only one hemin-related compound approved for use in the United States, although a different compound, heme arginate, is used in Europe and South Africa. Heme arginate is considered better because it tends to cause fewer side effects.
While these initial treatments are effective in managing acute attacks, some patients have recurring attacks. This is especially common in women, because attacks might be related to the menstrual cycle. In these cases, patients may have to be referred to a special porphyria service. Medications that prevent ovulation, like gonadotropin-releasing hormone analogs, may be helpful in preventing future attacks in women. A small number of patients with recurring attacks have also undergone a liver transplant.
Seizure control can be particularly complicated in patients with acute porphyrias, as many seizure medications aren’t suitable. Magnesium sulfate and diazepam are typically the first choices for controlling acute seizures. For severe, continuous seizures (known as status epilepticus), lorazepam can be used. If the patient has low sodium levels, these will need to be corrected with normal saline, being careful to consider the patient’s fluid balance. For long-term seizure control, gabapentin is used. If seizures last a long time, diazepam can be administered rectally.
Beta-blockers can be used to manage symptoms of autonomic dysfunction, which can occur with acute porphyrias. Any rapid increases in blood pressure require emergency medications like labetalol.
Finally, for any psychiatric symptoms or nausea during a porphyria attack, medications like chlorpromazine, a type of phenothiazine, can be given.
What else can Acute Porphyria be?
Porphyrias, a group of rare diseases, can show up in many different ways, so diagnosing them isn’t straightforward. Other conditions that might seem similar include lead poisoning, which can look a lot like an acute (sudden and severe) porphyria attack. Doctors can spot this by checking blood lead levels, even if another substance called zinc protoporphyrin is also high.
Sometimes, porphyria symptoms might be mistaken for a severe abdominal condition requiring surgery, or for an issue with women’s reproductive organs. It could also be confused with a stomach bug. But with porphyria, touching the belly doesn’t make the pain worse.
Other conditions that might look like porphyria include:
- Acute anemia (a quick drop in red blood cells)
- Hepatitis B and C (liver infections)
- Hodgkin lymphoma (a type of cancer that affects the immune system)
- Acute lymphoblastic leukemia (ALL, a type of cancer that affects white blood cells)
- Pediatric acute myelocytic leukemia (a type of childhood cancer that affects blood cells)
- Pediatric generalized anxiety disorder (excessive and persistent worry in children)
What to expect with Acute Porphyria
A few decades ago, patients with acute porphyria, a condition that includes neurological issues, faced a high mortality rate of 35%. Today, while the outlook for these patients remains cautious, the number of cases advancing to severe stages of the disease has decreased.
Possible Complications When Diagnosed with Acute Porphyria
There have been findings suggesting a link between acute porphyria and liver cancer, particularly in the case of Acute Intermittent Porphyria (AIP). AIP also has been found to increase the risk of high blood pressure and chronic kidney disease. Chronic pain is another problem associated with repeated attacks of acute porphyria.
Preventing Acute Porphyria
It’s important for patients to understand what can make their condition worse and what signs to look out for. Eating a diet high in carbohydrates can help manage the illness. Doctors should talk with patients about the importance of drinking enough fluids, which can help get rid of porphyrins, a type of harmful compound, in the body.
In situations where patients start experiencing high blood pressure, a diet low in salt, fat, and cholesterol is recommended.
Patients should also be warned to avoid activities that could cause dehydration, deplete their body of carbohydrates, and tire them out excessively.
