What is Acute Hepatic Porphyria?
Porphyrias are a group of metabolic disorders caused by a malfunction in one of the eight enzymes responsible for making heme, a component of blood. This malfunction results in the accumulation of organic compounds known as porphyrins, which leads to the specific set of symptoms typical for each porphyria. Hepatic porphyrias are those that occur when the enzyme deficiency takes place in the liver and include various types of porphyria, such as acute intermittent porphyria (AIP), variegate porphyria (VP), and others.
While these disorders are different, they all involve the accumulation of heme precursors. For the acute porphyrias that mainly affect the nervous system, symptoms seem to be triggered by an increased production of precursors toxic to the nervous system. On the other hand, chronic porphyrias, which mainly present with skin symptoms, seem to result from a buildup of porphyrins that make the skin sensitive to light. Some porphyrias can affect both the nervous system and the skin.
Treatment options include intravenous hemin to help control symptom progression. In severe cases of acute attacks or when symptoms progress despite hemin therapy, liver transplantation may be considered.
What Causes Acute Hepatic Porphyria?
Porphyrias are usually genetic conditions. They happen when a gene mutation affects the production of a substance called heme. Which type of porphyria someone has depends on which enzyme involved in producing heme is not working properly. The mutation responsible for porphyria can be passed down from parents to their children in different ways. Sometimes it’s an ‘autosomal dominant’ manner, which means only one parent needs to have the gene for the child to get the disease. Other times it’s ‘autosomal recessive’, which means both parents need to have the gene. There’s also a type passed on through the X chromosome.
There are several types of porphyria. For example, acute intermittent porphyria, variegate porphyria, and hereditary coproporphyria are autosomal dominant conditions and affect men and women equally. One very rare type, called aminolevulinic acid dehydratase deficiency porphyria, is autosomal recessive. For the autosomal dominant conditions, DNA tests in families have uncovered many different mutations.
The problem in porphyria is that not enough heme is produced. This leads to a build-up of other substances that are usually transformed into heme. Some types of porphyria, specifically the ones affecting the liver, can be set off by certain medications. These drugs are thought to interfere with the liver enzymes that help produce heme.
Risk Factors and Frequency for Acute Hepatic Porphyria
In the US, porphyria, a type of disease, affects about one in 25,000 people. Globally, this can vary between one in 500 to one in 50,000 people. Acute hepatic porphyrias, a form of the disease, affects all racial and ethnic groups. In many areas, the common type is AIP, while ALAD is the least common. Specifically, AIP affects about 5 to 10 in 100,000 people and the presence of AIP genetic mutations is seen approximately in one in 1675 individuals.
Another kind, VP, is rarer with a reported prevalence of 4 to 13 cases per million individuals. It is calculated that there are approximately three symptomatic cases per million individuals. Generally, these diseases are expected to affect both men and women equally as they are AD disorders. However, AIP tends to affect non-Hispanic women more, with reports showing that attacks are five times more frequent in women than in men.
Signs and Symptoms of Acute Hepatic Porphyria
Acute hepatic porphyrias are conditions characterized by sudden and long-term symptoms due to their impact on the central and peripheral nervous system. The most frequently reported symptom is a type of abdominal discomfort, rooted in nerve problems. The condition can affect several areas of the nervous system, resulting in a range of symptoms like a rapid heart rate, high blood pressure, muscle weakness, and loss of sensation. People with this condition may also experience pain in the back, chest, and limbs. A noticeable sign is abdominal pain with minimal physical findings.
The condition can be tough to diagnose because severe symptoms may not be taken seriously or may be overlooked due to the lack of clear physical signs. If a person has abdominal pain along with relatively normal physical examination results, but is also experiencing nervous system symptoms, further tests for acute hepatic porphyria should be conducted. This disorder comes in four types, with Acute Intermittent Porphyria (AIP) being the most common. The others are Variegate Porphyria (VP), Hereditary Coproporphyria (HCP), and ALAD-Deficiency Porphyria. VP and HCP may also cause blistering skin lesions.
A “classic triad” of symptoms are associated with acute porphyria: abdominal pain, changes in the central nervous system, and peripheral neuropathy (nerve damage leading to weakness, pain, and numbing). However, these symptoms are not specific to the condition, so they are often regarded as unrelated and not indicative of a unifying diagnosis.
Key Symptoms of Acute Hepatic Porphyrias include:
- Abdominal discomfort
- Autonomic changes such as fast heart rate and high blood pressure
- Muscle weakness
- Sensory loss
- Pain in the back, chest, and limbs
- Abdominal pain with minimal physical findings
- Possible blistering skin lesions in cases of VP and HCP
Testing for Acute Hepatic Porphyria
If doctors think someone may have acute hepatic porphyria, a rare liver condition, they’ll ask about the person’s medical history, carry out a physical check-up, and order some specific tests.
One very useful test checks for a substance called porphobilinogen (PBG) in the urine. This is both very accurate and sensitive. When the body isn’t producing enough heme, which is a key part of blood cells, more of heme’s building blocks like PBG are made instead. Nearly all people with acute hepatic porphyrias have a lot of PBG in their urine. However, this level can be nearly normal between attacks, so multiple tests might be needed during an attack to confirm a diagnosis.
Up to 90% of people who have the genes for the most common types of acute hepatic porphyrias don’t show obvious symptoms. That’s why, for these people, DNA or enzyme tests may be necessary to make a diagnosis.
Doctors may also check the person’s plasma and feces to measure the levels of ALA, PBG, and porphyrin (chemicals related to heme production). They also might examine the functioning of the person’s red blood cells. For example, they’ll check if there’s reduced activity of an enzyme called porphobilinogen deaminase (PBGD), which is common in about 90% of patients with acute hepatic porphyrias.
People with this condition often have low sodium levels in their blood, possibly because of overproduction of a hormone that controls water and salt balance, or because of loss of sodium from the gut or the kidneys. They may also have mild elevations in liver enzymes, although most other liver function tests usually remain within normal range.
Testing for these rare conditions isn’t typically available in all hospital labs as it requires special equipment, time, and expertise. Most of the time, blood, urine, and stool samples are sent off to a specialist lab for testing.
Treatment Options for Acute Hepatic Porphyria
The goal of treating a severe case of hepatic porphyria is to stop the attack quickly and provide supportive and symptomatic care until the attack subsides. This usually requires hospitalization. To properly treat the condition, doctors need to confirm that the patient is indeed suffering from acute porphyria. This is usually done by checking for high levels of a substance called urinary porphobilinogen (PBG) in the patient’s urine. This could have been detected either during the current health episode or in previous tests. It is crucial to know that the patient has acute porphyria, but knowing the exact type is not necessary.
When it comes to acute porphyria attacks requiring hospitalization, the patient may experience severe symptoms like intense pain needing strong pain relief medications, nausea, vomiting, different types of nerve damage, seizures, agitation, hallucinations, severe confusion, intestinal obstruction, low salt levels in the body, and more. In such scenarios, administering an intravenous medication called hemin is recommended. The recommendation for using hemin is due to the serious threat to life presented by a severe porphyria attack and the proven efficacy and safety of hemin. However, we don’t yet have data from large, high-quality clinical trials. A typical treatment plan involves giving hemin immediately upon confirmation of an acute porphyria attack, with a daily dose over four days.
To support the body’s recovery, a large intake of carbohydrates is advised alongside the hemin treatment, mainly to correct the body’s fasting state while waiting for the administration of hemin. Moreover, if the patient is diagnosed with low salt levels in their body (hyponatremia), emergency IV saline might be required.
For patients experiencing seizures (which can occur in 10% to 20% of cases), they can be controlled with specific medications, and in severe cases, sedation using the drug propofol can be deployed.
Liver transplantation is a last resort treatment and is only considered for patients with severe acute attacks of porphyria or if the symptoms continue to worsen despite hemin therapy.
In rare cases, a patient may experience frequent porphyria attacks over months or even years. This is particularly common in women, whose symptoms may appear monthly, a few days before menstruation. Doctors can help manage these frequent attacks with a hormone treatment that suppresses ovulation. Oral contraceptives are typically avoided because they can trigger acute attacks in some individuals. Regular infusions of hemin can provide reasonable control of symptoms under such circumstances. If neurological symptoms continue to worsen despite treatment, then the patient might be evaluated for a liver transplant.
What else can Acute Hepatic Porphyria be?
Acute hepatic porphyrias are health issues with vague symptoms that make them hard to diagnose. They are also not very common. Thus, doctors may initially mistake them for other health concerns. The main factors doctors consider when diagnosing are other sources of abdominal pain, other reasons for nerve tissue damage, mental health symptoms, seizures, other causes of liver disease or odd liver function tests, and other types of porphyrias. Like acute hepatic porphyrias, these conditions can also have nonspecific symptoms.
For instance, the nerve damage from acute porphyria might be wrongly identified as Guillain-Barré syndrome, a nervous system disorder. A brain scan (an MRI) might show results that look like a condition called posterior reversible encephalopathy syndrome (PRES). This goes to show how significantly acute porphyria can impact the brain. In situations like these, doctors recommend testing for porphyria to rule it out as a potential cause of the symptoms.
What to expect with Acute Hepatic Porphyria
Acute hepatic porphyrias are relatively rare and mild, which means there’s limited information about the long-term outlook for people with this condition. It’s believed that mortality rates are higher in patients with severe symptoms. However, many people with milder versions of the disease may never be diagnosed, which could lead to an overestimation of the mortality rate.
Generally though, patients can have a positive outlook, especially if their disease remains inactive and the sudden onset of symptoms (acute attacks) are promptly diagnosed and treated.
Possible Complications When Diagnosed with Acute Hepatic Porphyria
: Acute hepatic porphyrias can lead to very serious health problems if not treated immediately. People with this condition can suffer from sudden episodes of severe symptoms like abdominal pain, frequent nausea and vomiting, dangerously high blood pressure, and an extremely fast heart rate. The most intense moments can include nerve-related symptoms such as muscle weakness, which may lead to complete body paralysis, as well as brain-related symptoms like seizures and coma, and occasional psychological symptoms like anxiety, hallucinations, and severe mental confusion. However, these symptoms usually go away once the episode ends.
Additionally, people suffering from acute hepatic porphyrias are prone to high blood pressure, continual kidney failure, liver cancer, and iron deficiency anemia due to menstrual blood loss (which can occur in women without this condition too) or excessive iron from frequent hemin therapy. Hence, it’s important to manage high blood pressure, avoid medications that can harm the kidneys, undergo liver imaging for people over 50 years to detect liver cancer early, and monitor blood ferritin levels regularly.
Acute hepatic porphyrias can lead to very serious health problems if not treated immediately. People with this condition can suffer from sudden episodes of severe symptoms like abdominal pain, frequent nausea and vomiting, dangerously high blood pressure, and an extremely fast heart rate. The most intense moments can include nerve-related symptoms such as muscle weakness, which may lead to complete body paralysis, as well as brain-related symptoms like seizures and coma, and occasional psychological symptoms like anxiety, hallucinations, and severe mental confusion. However, these symptoms usually go away once the episode ends. Additionally, people suffering from this condition are prone to high blood pressure, continual kidney failure, liver cancer, and iron deficiency anemia due to menstrual blood loss or excessive iron from frequent hemin therapy.
Common Health Concerns:
- High blood pressure
- Chronic kidney failure
- Liver cancer
- Iron deficiency anemia from frequent menstruation
- Iron overload from frequent hemin therapy
Health Recommendations:
- Control high blood pressure
- Avoid kidney-damaging medications
- Regular liver imaging for those over 50 years old to detect liver cancer early
- Regular monitoring of blood ferritin levels
Preventing Acute Hepatic Porphyria
For people suffering from sudden attacks of hepatic porphyrias, a liver disorder, avoiding certain triggers can help treat the condition and even prevent further attacks. Some people can predict what factors trigger their attacks and should try to avoid or lessen these as much as possible.
During a sudden attack, people should stop taking medications that could potentially cause harm. It’s highly recommended that doctors check the websites of the American Porphyria Foundation and the European Porphyria Network. These websites regularly update lists of medications, including some that may not be clearly categorized, and provide reasons for their classifications. They are valuable resources for avoiding prescribing damaging drugs when treating other diseases or symptoms at the same time.
Lifestyle choices like smoking and drinking alcohol can also cause harm. Therefore, patients should be advised to stop smoking, including marijuana, and to avoid drinking alcohol. Both smoking and alcohol consumption can worsen hepatic porphyrias by affecting the liver’s enzymes and reducing its heme (an essential component of human blood), leading to an increase in the production of harmful heme precursors.
Acute attacks have also been associated with certain hormones (like progesterone), a lack of calorie or carbohydrate intake (particularly fasting), and the metabolic stress arising from infections or other illnesses.
