Key Takeaways
- Acute hepatic porphyria (AHP) is a group of rare genetic disorders that affect the liver’s ability to produce heme, a vital component of blood, and can manifest with a variety of symptoms often confused with other conditions.
- Diagnosing AHP can be challenging due to its diverse symptoms, but it typically involves urine and genetic tests to confirm the condition.
- While there is no cure for AHP, managing triggers and using treatments like hemin infusions or givosiran can help prevent acute episodes and improve the quality of life for those affected.
Porphyria is a group of rare disorders characterized by a buildup of porphyrins in the body, the symptoms of which are often misdiagnosed due to their similarities with other conditions.
Porphyrins are natural chemicals that the body needs to make heme, which is a part of hemoglobin. Hemoglobin is a specific protein in red blood cells responsible for carrying oxygen to the body’s organs and tissues.
The body needs different enzymes to convert porphyrins into heme, and if there aren’t enough, porphyrins can build up, leading to significant health implications.
Symptoms of porphyria can vary by type and severity, and although there’s no cure, managing triggers, medications, and certain lifestyle adaptations can help with overall condition management.
There are four main types of acute porphyria:
- acute intermittent porphyria (AIP)
- variegate porphyria (VP)
- hereditary coproporphyria (HCP)
- ALAD-deficient porphyria (ADP)
AIP is the most prevalent form of porphyria, affecting roughly
Let’s look at each of them in more detail.
Acute intermittent porphyria (AIP)
AIP is the most common acute porphyria, accounting for around 80% of cases. Symptoms typically begin in adulthood and are more common in females.
Symptoms and complications
Abdominal pain is the most common symptom of AIP. Other symptoms include:
- gastrointestinal symptoms, such as constipation or nausea
- intense pain
- feeling weak
- mental health changes, such as anxiety, agitation, and insomnia
- hallucinations
- delusions
- seizures
Some people may also develop photosensitivity, an atypical skin reaction to sunlight or artificial ultraviolet (UV) light, though this generally occurs only in those with advanced kidney failure.
Long-term AIP complications can include progressive kidney damage, hypertension (high blood pressure), and an increased risk of liver cancer, though constant monitoring significantly improves outcomes.
AIP is caused by a variant in the gene for the third enzyme in the heme pathway, porphobilinogen deaminase (PBGD), also known as hydroxymethylbilane synthase (HMBS).
Inheritance is autosomal dominant (inherited from one parent). Most people with the variant won’t ever experience symptoms, a state known as latent AIP.
While some may experience only a few acute episodes, a minority will experience frequent episodes that may be accompanied by persistent, chronic symptoms.
Many triggers of AIP episodes can increase the production of the first enzyme in the heme pathway, delta-aminolevulinic acid synthase-1 (ALAS1). This can lead to a buildup of toxins called delta-aminolevulinic acid (ALA) and porphobilinogen (PBG), which are associated with neurological symptoms.
Variegate porphyria (VP)
VP is the second most common acute porphyria. While the symptoms of acute episodes mirror those of AIP, blistering skin lesions occur more commonly in VP than in acute episodes.
This type is caused by a variant in the gene for the seventh enzyme in the heme pathway, called protoporphyrinogen oxidase (PPOX).
Like AIP, inheritance is typically autosomal dominant, with symptoms usually appearing after puberty.
In very rare cases, people may inherit a PPOX variant from each parent (autosomal recessive inheritance), which causes severe illness from an early age.
Hereditary coproporphyria (HCP)
HCP is less common than VP, but acute episodes can cause the same symptoms. However, skin effects like blistering are much less common than in VP.
HCP is caused by a variant in the gene for the sixth enzyme in the heme pathway, called coproporphyrinogen oxidase (CPOX).
Inheritance is autosomal dominant, and many people with the CPOX alteration will never develop symptoms.
In very rare cases, people may inherit a CPOX alteration from each parent, which can lead to very intense symptoms from childhood.
ALAD-deficient porphyria (ADP)
ALAD porphyria (ADP) is an extremely rare condition. There have been only around 12 well-documented cases, most of which have involved males, although experts have been unable to identify a reason for this.
ADP inheritance is autosomal recessive, meaning the altered gene is inherited from both parents.
Symptoms of ADP are the same as AIP but may begin in childhood or adolescence.
AHP can cause many symptoms that can be similar to those seen in other health conditions, and symptoms may often seem unrelated, which is one of the reasons it can often be misdiagnosed.
If you have AHP, you may experience severe acute episodes, but you may also experience chronic symptoms in between episodes.
Common symptoms may include pain in the:
- abdomen
- back
- chest
- limbs
Other systems affected and the accompanying symptoms may include:
Digestive problems, such as:
- indigestion
- vomiting
- nausea
- constipation
- diarrhea
Symptoms of the central nervous system, such as:
- depression
- anxiety
- insomnia
- hallucinations
- seizures
Symptoms of the peripheral nervous system, such as:
- fatigue
- numbness
- tingling
- muscle weakness
- paralysis
Some people
Those with HCP and VP may experience skin photosensitivity (sensitivity to sunlight), leading to blistering and excess body hair growth.
Additionally, people may notice that their urine is reddish or brown.
AHP is a genetic condition. This means that the primary risk factor is inheriting an altered gene from one or both parents.
There are
- medications
- hormonal changes
- specific diets, such as those that include fasting
- alcohol consumption
- smoking
- physical and emotional stress
Three groups of symptoms, known as the “classic triad,” may suggest AHP. These include abdominal pain, central nervous system irregularities, and peripheral neuropathy.
Healthcare professionals will then typically use blood and urine tests to confirm a diagnosis.
First-line diagnostic testing may include a urine test to test for PBG and porphyrin levels. DNA testing can provide further confirmation of diagnosis.
Diagnosis is often difficult due to the range of symptoms that people can experience and the similarity to many other health conditions. Some of the conditions that someone may be misdiagnosed with may include:
Although there’s no cure for AHP, there are ways to manage symptoms.
If you experience an acute episode, your healthcare team may suggest admission to the hospital for treatment of immediate symptoms, such as pain or breathing difficulties. Treatment may include intravenous (IV) glucose and a hemin infusion.
Hemin (Panhematin) is the most common AHP treatment and is generally prescribed if IV glucose hasn’t worked. However, your doctor may prefer to use Hemin right away to avoid waiting for a glucose response.
As a biologic medication, Hemin is produced in a lab from biological materials rather than a mix of chemicals following a specific recipe. Specifically, it’s derived from processed human red blood cells.
While Hemin (Panhenatin) alone has not yet been fully established as a preventive measure, the Food and Drug Administration (FDA) approved givosiran (Givlaari) in 2019 for the management of AHP episodes.
Givosiran helps prevent the buildup of toxins in the body, which, in turn, helps reduce the frequency of AHP episodes.
If you have AHP, you may experience no symptoms at all outside of acute episodes, and avoiding triggers may be the best way to manage the condition.
However, some people with AHP may experience chronic symptoms, such as:
- fatigue
- pain
- indigestion
- constipation
A 2022 study found that the impacts of AHP on daily life were:
- difficulties performing general daily activities
- difficulty exercising
- negative impacts on work
- special dietary requirements
- anxiety
- depression
Working with your healthcare team to manage chronic AHP symptoms, recognizing and avoiding triggers, and seeking prompt medical help for acute episodes is important for maintaining a good quality of life.
The outlook for AHP depends on your specific type of porphyria and its severity. For most, the outlook and survival rate are similar to those without AHP.
If your body continuously produces too much ALA and PBG, there may be a higher risk of developing systemic hypertension, chronic kidney disease, and liver cancer, which can all affect survival rates.
The importance of long-term monitoring can’t be overstated. Your healthcare team will likely suggest:
- annual liver disease checks
- liver cancer (specifically hepatocellular carcinoma) screenings, beginning at age 50, with a liver ultrasound every 6 months
- annual chronic kidney disease checks, to include serum creatinine and estimated glomerular filtration rate
- counseling on chronic and long-term AHP complications of AHP and the need for long-term monitoring
Typically, if you receive an early diagnosis and are treated quickly, you can lead a healthy life.
AHP is a rare but serious group of genetic disorders that affects the liver’s heme production. Heme is an essential element of the blood.
The condition can cause acute episodes, with symptoms including severe abdominal pain, nausea, and muscle weakness. Triggers of AHP can include medications, physical and emotional stress, and hormonal fluctuations.
Diagnosis is typically performed through urine and genetic testing, while treatment focuses on managing and preventing acute episodes.
Early diagnosis and thorough medical care are essential for maintaining quality of life and providing a positive outlook.