A mutation that impacts an enzyme involved in heme biosynthesis causes porphyrias, which are inheritable metabolic disorders. There are different types of porphyrias based on the specific enzyme affected, but acute intermittent porphyria (AIP) is the most common and severe type.
Read on to find out more about AIP and how it affects the body, as well as its diagnosis and treatment.
AIP is a rare metabolic disorder whose hallmark is a partial deficiency of an enzyme called hydroxymethylbilane synthase.
People with AIP have high levels of porphyrins and porphyrin precursors because the disorder doesn’t allow the body to have enough enzymes to create heme, which is a part of hemoglobin. An HMBS gene mutation causes the disorder.
What is heme?
Heme is a necessary molecule for living things. It is the precursor to hemoglobin, which is essential to attach to oxygen in the bloodstream. It
AIP manifests as attacks or episodes, which can include abdominal pain, gastrointestinal problems, and nerve problems like neuropathy. Sometimes other symptoms can include:
Certain symptoms, especially occurring concurrently, can raise suspicion for possible AIP. One of those symptoms is unexplained abdominal pain, especially with psychological symptoms, muscle weakness, or low sodium levels. The other symptom is reddish or dark urine, which can occur with other symptoms.
Diagnosis of AIP can be tricky because the symptoms occur periodically and can sometimes be nonspecific. Doctors usually diagnose AIP by looking for characteristic symptoms during an attack or through a medical history and performing a clinical exam and some lab tests.
Clinical testing can include screening tests to measure levels of porphobilinogen (PBG), which is a porphyrin precursor in the urine. High levels of PBG link to AIP attacks. Doctors can also perform genetic testing to find an HMBS gene mutation, which may prompt various family members to receive testing.
Doctors diagnose AIP
If symptoms are characteristic of AIP, a medical professional may consider this condition.
Outside factors, like medications, alcohol, hormonal changes, or insufficient calorie intake, typically trigger episodes of AIP when symptoms occur. The attacks usually last about a week, with symptoms
- severe abdominal pain with constipation and vomiting
- psychiatric symptoms, such as depression
- peripheral neuropathies, including weakness in lower extremities that moves up
- central nervous system impairment, such as delirium, weakness progressing to quadriplegia, cortical blindness, coma
In between attacks, many people report being symptom-free, but
With treatments, you can manage the condition. But if the AIP does not respond to heme therapy and keeps recurring, the only cure currently available is an orthotopic liver transplant.
Some medications can be triggers for AIP if someone has a genetic mutation for it. Triggers can be different for each person, and susceptibility to triggers can change over your lifetime.
Medications that encourage heme production in the liver may be triggers, and it’s important to avoid certain medications.
Medications to avoid may
- valproic acid
Talk with your doctor about what medications to avoid if you have a diagnosis of AIP or suspect that you might have it.
Treatment for AIP depends on the symptoms. While people can vary in attack severity, without proper diagnosis and appropriate treatment, symptoms can progress to life threatening complications.
The goal of treatment is to manage symptoms, avoid complications, and stop heme production in the liver.
Different specialists may form the treatment team, collaborating to address all the symptoms. Those specialists can include pediatricians, neurologists, hematologists, and psychiatrists.
Some treatment options might include:
- stopping any drugs that can cause AIP attacks
- getting enough calories and nutrients, including glucose and salt, even via intravenous (IV)
- increasing carbohydrate intake
- taking pain relievers to help with mild attacks
What medications can help with pain from acute intermittent porphyria?
Parenteral opiates can help with pain, and anti-emetics can help with nausea. You can manage tachycardia and hypertension with beta-blockers or calcium channel blockers, and you can manage seizures with diazepam or clonazepam.
The only cure currently available for AIP is an orthotopic liver transplant. This involves removing the diseased liver and replacing it with a healthy liver or part of one from a donor.
An orthotopic liver transplant has a survival rate of about
AIP is an inheritable condition associated with enzymes affecting the heme biosynthesis pathway. It causes attacks with symptoms that can affect various systems of the body, and without accurate diagnosis and treatment, it can cause severe, even life threatening complications.
But you can manage the condition, especially if you receive an early diagnosis and prompt treatment. Treatment usually focuses on relieving specific symptoms, as well as IV heme therapy. While there is currently no cure, a liver transplant may be possible.