Acute Intermittent Porphyria

Acute intermittent porphyria (pronounced “por-FEER-ee-uh”) is a genetic disorder. It causes chemicals called porphyrins and porphyrin precursors to build up in cells throughout your body, especially your liver, blood and bone marrow.

Your body needs a certain amount of these chemicals to make heme (a building block of hemoglobin in your red blood cells). But with acute intermittent porphyria (AIP), the chemicals build up to abnormal levels. This can harm your body, leading to painful symptom attacks that come on quickly and tend to last no more than a few days if treated (acute), as well as other issues.

Although AIP is the most common type of acute hepatic porphyria, providers consider it a rare disease overall. The gene variations that cause AIP pass down within biological families. Most people who inherit the gene changes never develop symptoms. But if you’re one of the few who do develop symptoms, you know what a toll they can take on your life.

Thankfully, researchers continue to find new ways to treat attacks when they happen and lower the risk of future attacks. Your provider can help you manage this condition — and all the stress and anxiety that may come along with it.

Acute intermittent porphyria symptoms

AIP causes symptom attacks. Severe abdominal pain is the most common symptom during such attacks.

Other possible symptoms include:

• Altered mental state, including agitation or confusion
• Fast heart rate, heart palpitations and raised blood pressure
• Hallucinations
• Muscle weakness
• Nausea and vomiting
• Pain — possibly severe — in your arms, legs or back
• Seizures
• Trouble pooping (constipation) and/or peeing (urinary retention)
• Trouble sleeping (insomnia)

On occasion, your urine could be discolored/dark red or reddish brown, especially if the sample isn’t fresh or is exposed to light.

An attack might include just a few or many of these symptoms. AIP affects everyone a little differently. You may have just one attack, a few or many throughout your life.

There’s such a wide range of symptoms because the chemicals that build up in AIP affect your nervous system. This is your body’s command center. It controls everything from digestion and heart rate to mental function and muscle movement. The chemical buildup is toxic to your nerve cells and can affect how they work, leading to many possible symptoms.

Symptomatic AIP is more common among females. This may be due to hormonal changes associated with menstruation. Symptoms usually start after puberty, typically in your 20s or 30s. It’s rare for symptoms to begin in childhood.

Acute intermittent porphyria causes

AIP is a genetic condition. That means you’re born with certain changes to your genes that cause the disease. But having gene changes doesn’t mean you’ll develop symptoms. Other things — like hormonal changes and medications — trigger symptoms to start in people with genetic susceptibility. Let’s take a closer look at how this works.

AIP genetics

If you have AIP, you’re born with a gene change that affects how your body makes heme (pronounced “heem”). Specifically, there’s a change to one of your HMBS genes that causes it not to function. This gene tells your body how to make an enzyme called hydroxymethylbilane synthase (also known as porphobilinogen deaminase, or PBG-D).

So, why do you need this enzyme? It’s one of many enzymes that move the heme-making process along — similar to how an assembly line works. PBG-D joins together molecules of porphobilinogen (PBG). After these molecules join up, they keep moving down the assembly line. And other enzymes change them in various ways until heme is formed.

When you have changes to your HMBS gene, your body can’t make enough PBG-D. When you don’t have enough of this enzyme, the whole assembly line process gets thrown off. Instead of joining together and moving down the line, PBG molecules and another chemical called ALA hang around and start building up in your cells. This buildup leads to the symptoms of AIP.

Experts don’t fully understand why some people with these gene changes develop symptoms while others don’t. But they believe certain “triggers” may cause your first AIP attack — and possibly more attacks down the road.

AIP attack triggers

Triggers are things that make an AIP attack start. They can vary widely from person to person. What triggers an attack for one person might not do anything to you.

Possible triggers include:

• Caloric or carbohydrate restriction (certain forms of dieting or fasting)
• Certain medications, especially barbiturates, sulfonamides, oral contraceptives and anti-seizure medications
• Excessive alcohol use
• Hormonal changes (for example, with menstruation)
• Infections
• Recreational drug use
• Stress

If genetic testing shows you have gene changes associated with AIP, your provider will talk to you about possible triggers and ways to avoid them.

Complications of AIP

The chemicals that build up in your cells can damage tissues and organs, leading to complications like:

• Chronic kidney disease and kidney failure
• Chronic liver disease
• Chronic pain due to nerve damage
• High blood pressure
• Liver cancer (usually hepatocellular carcinoma)

How doctors diagnose AIP disease

Healthcare providers diagnose AIP by:

• Doing a physical exam
• Talking to you about your symptoms, medical history and biological family history
• Collecting a sample of your urine (pee) to check PBG levels
• Possibly testing samples of your blood or stool (poop) to see if elevated PBG levels are due to AIP or another type of porphyria

Your provider may recommend genetic testing. This can establish a clear genetic link that allows your biological family members to get referrals for genetic counseling.

How is acute intermittent porphyria treated?

Treatment depends on the severity of your AIP attacks and how often you get them. When an attack strikes, you’ll likely need care at a hospital to manage symptoms and prevent complications. At the hospital, providers may give you:

• Hemin injections (Panhematin®) to stop the attack (by reducing porphyrin and porphyrin precursor levels)
• Medications to manage pain, nausea, seizures or other symptoms
• IV fluids and nutrients

Providers will keep a close eye on you and watch for any signs of complications. You may need respiratory support (mechanical ventilation) if your muscles that control breathing are too weak.

Once the attack has ended, your provider may talk with you about long-term treatment options. Medications are available to help lower your risk of future attacks and/or make them less severe. For example, your provider may prescribe routine:

• Givosiran injections
• Panhematin injections
• Hormone therapy (gonadotropin-releasing hormone analogues), if attacks recur with menstruation

Your provider can tell you more about these medications, how they work and whether they might help you. If you’re interested in joining a clinical trial, your provider can tell you more and help you find options.

When should I see my healthcare provider?

Go to an emergency room or urgent care if you believe you’re having an AIP attack. The sooner you receive medical care, the better your chances of shortening the attack and lessening its severity.

If you’ve been diagnosed with AIP, it’s a good idea to wear a medical alert bracelet or carry a card in your wallet that verifies your diagnosis. Depending on the type of phone you have, you may be able to add emergency information to your phone’s lock screen. These small steps can allow you to get proper emergency treatment when needed. ER or urgent care providers may not be familiar with porphyria. So, they may look for other causes of your symptoms (and possibly not be able to find any).

Your healthcare provider can give you further advice on how to get care right away when you need it. They’ll also tell you when to come in for follow-ups. These follow-ups are important for keeping an eye on your condition and checking for signs of complications.

Ideally, establish care with a provider at a medical facility that has a porphyria center. Such centers have experts familiar with porphyria who are able to offer the latest guidance and treatment options.

What can I expect if I have AIP disease?

Your healthcare team can give you the most accurate picture of your prognosis (outlook). In general, acute intermittent porphyria isn’t usually fatal. People who are diagnosed early enough — before attacks cause severe nerve damage — have a good prognosis. This is because early treatment of attacks and efforts to prevent future attacks can help protect your body from disease complications.

Some people need liver and/or kidney transplants to manage organ failure. Such options are usually a last resort when other treatments aren’t working.

Will my children inherit AIP?

It’s possible. Your body’s genetic code (genome) contains two copies of the HMBS gene. One is normal, and the other is abnormal. Which copy gets passed on to your child is totally random. This means if you have AIP, each of your children has a 50% chance of inheriting it. It’s like a coin toss.

If the abnormal copy gets passed on to your child, they’ll have AIP and may possibly develop symptoms at some point. If your child inherits the normal copy (and they also inherit a normal copy from their other parent), they’ll never develop AIP. And there’s no chance of them passing it on to their own children.

AIP passes down within families in an autosomal dominant way. This means it takes just one copy of an abnormal gene — from either biological parent — for a child to inherit the disease.

Genetic counseling can help you learn more about how AIP and other porphyrias are inherited. You may decide to have your children tested for gene changes associated with AIP — even if they don’t show symptoms. If they’ve inherited AIP, their healthcare providers can help them avoid triggers (and possibly prevent symptom attacks) throughout life.