Acute hepatic porphyria (AHP) is a group of genetic conditions that affect the nervous system and skin. AHP causes painful and sometimes life-threatening attacks of symptoms. It's part of a group of eight inherited disorders called porphyrias.
Porphyrias are very rare. Only about 5 out of every 100,000 people have these conditions.
Some people with AHP have few to no symptoms or problems. Others have frequent, severe attacks throughout their lifetime. These attacks can affect every part of your life, including your job and relationships. But there are treatments to manage them.
What Is Acute Hepatic Porphyria (AHP)?
AHP is a group of rare hereditary diseases. One or both parents pass them down to their children.
Porphyrins are compounds your body uses to make heme, which is an important part of the protein hemoglobin. You need hemoglobin in your blood to carry oxygen to your organs and tissues. People with porphyrias are missing one of the enzymes needed to make heme. A different enzyme is missing in each of the four types of AHP.
Hepatic refers to the liver. In AHP, the enzyme you need to make heme is missing from your liver. Because your body can't make heme, other substances that would normally go into making heme aren't used. These substances, including porphobilinogen and aminolevulinic acid, are toxic. They build up in your liver. Then they travel through your bloodstream and damage your nerves.
The nerve damage leads to attacks of pain, numbness, nausea, skin changes, and other symptoms. Symptoms vary from person to person depending on which parts of the body AHP affects.
Most people have only a few attacks during their lifetime. Around 1 in 10 people have at least four attacks per year. Some attacks are severe enough to need treatment in a hospital. AHP can be life-threatening.
Types of Acute Hepatic Porphyria (AHP)
There are four types of AHP. In each type a different enzyme is missing, but all four affect the liver and nerves.
Acute intermittent porphyria (AIP)
This is the most common type, affecting about 80% of people with AHP. When you have AIP, you're missing some of the hydroxymethylbilane synthase (HMBS) enzymes. A change called a mutation to the HMBS gene causes this type. Some people inherit the mutation from a parent. In others, the change just happens randomly.
ALAD-deficiency porphyria (ADP)
A change to the delta-aminolevulinic acid dehydratase (ALAD) gene causes an almost total lack of the enzyme with the same name. You need to inherit this gene mutation from both of your parents to have ADP.
ADP is so rare that only about 10 cases have been diagnosed in the entire world. Almost all of them were diagnosed in people who were men or assigned male at birth (AMAB). ADP is different from other types of AHP, which mainly cause symptoms in those who are female or were assigned female at birth (AFAB).
Hereditary coproporphyria (HCP)
The enzyme that's missing in this type is coproporphyrinogen oxidase (CPOX). The mutated CPOX gene is either inherited from one parent or it happens on its own. Many people with HCP don't have symptoms.
Variegate porphyria (VP)
People with the VP type are missing the enzyme protoporphyrinogen oxidase (PPO or PPOX). A mutation that's either passed down from one parent or that happens randomly causes VP.
Having one of the gene changes that cause AHP doesn't necessarily mean you'll have symptoms. Only about 1 in 10 people who've inherited an AHP gene have attacks. Some people have no symptoms or just a few attacks during their lifetime. Others have frequent attacks that are severe enough to put them in the hospital and disrupt their daily life.
Causes of Acute Hepatic Porphyria (AHP)
AHP is a genetic condition. Because of a gene mutation, you don't have the enzymes your body needs to make heme. The ingredients used to make porphyrin build up in your liver and get into your bloodstream.
Genes set you up for the disease. Then something in your environment triggers attacks by increasing your need for heme.
These are some common AHP triggers. Avoiding or reducing your exposure to them can help prevent attacks:
Hormone changes. Often the first signs of AHP appear after puberty, when hormone levels change. Women may experience attacks during other times of hormonal changes, such as during their menstrual periods, in pregnancy, and during menopause. Certain types of birth control medications, including low-dose estradiol and low-dose estrogen-progestins, can help prevent attacks related to your periods.
Medications. Some over-the-counter, prescription, and recreational drugs trigger attacks by increasing the production of porphyrin. These medicines include:
- Carbamazepine (Carbarol, Tegretol, Tegretol XR), phenytoin (Dilantin), and valproic acid (Depakote) – drugs that treat seizures
- Danazol, a treatment for endometriosis
- Diclofenac, a nonsteroidal anti-inflammatory drug (NSAID) used to relieve pain
- Hormones like estrogen and progesterone
- Marijuana and other recreational drugs
- Metoclopramide (Reglan), a treatment for gastroesophageal reflux disease (GERD) and nausea
- Rifampin (Rifadin), a tuberculosis treatment
- Sulfonamide antibiotics
Heavy alcohol use. Drinking is another known trigger, especially binge drinking. Try to avoid alcohol. If you do drink, don't have more than one glass of alcohol a day if you're female, and no more than two drinks a day if you're male.
Infections. Certain infections can set off symptoms, including:
- Hepatitis C
- HIV
- Urinary tract infections (UTIs)
- Pneumonia
- Shingles
Staying up to date on your vaccines can help you avoid these and other infections. When you're sick, it's important to treat both the infection and the AHP attack.
Extreme diets. Fasting or eating a very low-calorie or low-carbohydrate diet can lead to attacks. Obesity might also contribute to symptoms. When it comes to eating, moderation is key. No foods are off-limits, but things like broiled meat, Brussels sprouts, and cabbage in large amounts might increase porphyrin production. A dietitian can help you figure out which foods might be causing your symptoms.
Smoking. Along with its other health risks, smoking boosts the amount of toxic heme ingredients in your blood. If you smoke, ask your doctor for advice on how to quit.
Stress. It's not only emotional stress that triggers AHP symptoms. Physical stressors such as surgery or a lack of sleep are also linked to attacks. Managing stress with the relaxation technique that works best for you may help to reduce the number and severity of attacks.
Who's Most at Risk for AHP
Anyone can inherit an AHP gene mutation if one or both of their parents carries it. AHP affects people of all races and ethnicities, although it is more common in White people.
It also affects men and women equally, but women are much more likely to have symptoms, possibly because of their hormones. About 80% of those who have symptoms of AHP are women in their teens to 40s.
AHP Symptoms
How can you know if you have AHP? Because this condition affects so many parts of your body, its symptoms are easy to confuse with those of other diseases.
Some people with AHP don't have symptoms. Others have attacks of symptoms that are severe. Belly pain is the most common symptom. It can last anywhere from a few hours to a few days. Up to 95% of people who get AHP attacks have pain in this area.
Which other symptoms you have depends on the parts of your nervous system that are damaged.
Central nervous system (brain and spinal cord):
- Anxiety
- Depression
- Confusion
- Memory loss
- Tiredness
- Seizures
- Hallucinations
Peripheral nervous system (nerves that send information between your brain and body):
- Nerve pain
- Muscle weakness
- Paralysis
- Trouble breathing
Autonomic nervous system (the part that controls organs like your heart, stomach, and lungs):
- Pain in the belly
- Chest or back pain
- High blood pressure
- Fast or irregular heart rate
- Low sodium in the blood, called hyponatremia
- Nausea and vomiting
- Constipation
Skin
- Blisters when the skin is exposed to sunlight (only in VP and HCP)
- Itching
- Excess hair growth
- Swelling
- Scarring
Other possible symptoms are:
- Brown or red urine
- Difficulty emptying your bladder
Given how rare AHP is, these symptoms are more likely to be from a more common condition. But if you get frequent attacks of these types of symptoms, see your doctor to find out what's causing them.
Show Sources
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American Liver Foundation: "Acute Hepatic Porphyria (AHP)," "ALAD Deficiency Porphyria (ADP), "Variegate Porphyria (VP)."
American Porphyria Foundation: "ALAD-Deficiency Porphyria (ADP)."
BMJ Open Gastroenterology: "04142 Sleep and Stress in Patients with Acute Intermittent Porphyria."
Cleveland Clinic: "Acute Hepatic Porphyria," "Diet Information for All Porphyrias."
International Foundation for Gastrointestinal Disorders: "Triggers for Acute Attacks in Acute Hepatic Porphyria."
Molecular Genetics and Metabolism: "Acute Hepatic Porphyrias: Recommendations for Diagnosis and Management with Real-World Examples."
Orphanet Journal of Rare Diseases: "Challenges in Diagnosis and Management of Acute Hepatic Porphyrias: From an Uncommon Pediatric Onset to Innovative Treatments and Perspectives."
StatPearls: "Acute Hepatic Porphyria."
UTSouthwestern Medical Center: "Porphyria."
