The genes that each of us inherit from our parents will impact the course of our lives forever. Some people will be genetically predisposed to be tall or to have curly hair, and some individuals will be more susceptible to inheriting certain diseases or health conditions. Acute Intermittent Porphyria (AIP) is a rare metabolic disorder that consists of the deficiency of the enzyme hydroxymethylbilane synthase (HMBS).1 The deficiency of this enzyme can cause the accumulation of toxic heme metabolites aminolevulinic acid (ALA) and porphobilinogen (PBG) in the body.5
AIP is part of the group disorders known as porphyrias, which includes hereditary coproporphyria, aminolevulinic acid dehydratase deficiency (ALAD) porphyria and variegate porphyria.2 This group of diseases affect primarily the nervous system or the skin, and sometimes the liver and other organs.2 If an individual has a type of porphyria, he or she does not develop the other types.
This is an autosomal dominant disease, which means that the disease can be transmitted from any of the parents to the child.1 The disease by itself does not produce symptoms, and some patients will never present any symptoms in all their lives.3 AIP is usually triggered by external factors such as excess alcohol consumption, infections, use of specific drugs, hormonal changes or dietary changes.3 AIP is also known as Swedish porphyria.
Causes of acute intermittent porphyria
The main cause of Acute Intermittent Porphyria is the mutation in the HMBS gene that is passed on by the parents to the child. As mentioned before, AIP is a multifactorial disorder, meaning that diverse factors, such as genetic and environmental factors, need to occur simultaneously for symptoms to appear.3 These factors are called triggers, and they vary depending on each individual and time.3
Signs and symptoms
An AIP patient can experience a range of different symptoms and physical findings that can potentially affect multiple organs of the body.4 The severity and frequency of the outbreaks of symptoms vary from one person to another; if undiagnosed properly, the symptoms can provoke life-threatening complications.4 The symptoms of the disease occur as episodes or “attacks” that can develop within hours or days.4
The symptoms usually appear after puberty, especially in the case of women, due to the hormonal changes that take place during the menstrual cycle.4 In some cases, the levels of sodium and chloride in the body decrease and contribute to the symptoms of AIP. Some of the symptoms are:4
- Abdominal pain
- Muscle weakness
- Pain in the back, arms and legs
- Palpitations and increased blood pressure
- Urinary retention
- Seizures, hallucinations and confusion
It is important to identify when an acute episode or attack is happening to be treated properly– otherwise, the recovery can take much longer, lasting from weeks to months.
- An extensive clinical evaluation: This will help determine the symptoms, duration, frequency and triggering factors.
- Symptom assessment.
- Specialized laboratory tests:
- Genetic testing: Genetic testing is used to determine if other family members have the disease and advise of the potential risk of possible acute attacks.4
- Urine porphyrin analysis: It is important to screen the levels of the porphyrin precursor porphobilinogen to confirm a diagnosis of acute porphyria.4
- Blood and faecal porphyrin levels: It is necessary when there are high levels of PBG in the urine analysis.5
- Detailed patient history
AIP can mimic symptoms of other diseases so it is important to test for similar diseases to discard them. Some similar disorders can be Cuillain-Barré syndrome, Tyrosinemia type I and lead toxicity.5 Patients are highly recommended to seek consultation with a porphyria specialist at the moment of their diagnosis.
Management and treatment of acute intermittent porphyria
The management and treatment of AIP are directly targeted to the symptoms that each patient presents. The treatment revolves around the severity of the symptoms and if it is considered an acute attack.2 Depending on the case, the treatment may need the coordinated efforts of diverse specialists, including neurologists, hepatologists, paediatricians and psychiatrists.4 The treatment for AIP includes the use of hematin to reduce the production of porphyrin precursors to prevent complications and suppress heme creation in the liver.3
Part of the treatment for AIP also consists of avoiding medication that can lead to an attack or worsen the symptoms that already exist and ensuring that the patient has a correct caloric intake.3 In case of an acute attack, the patient may need:3
- Adequate caloric support
- Correction and monitoring of electrolytes
- Discontinuing porphytogenic agents
- Hemin or glucose infusion
Risk factors and complications
Some of the complications that can happen due to AIP are:
- Misdiagnosis and delayed treatment: AIP can be difficult to diagnose due to the rarity of the disease and as it can be confused with other diseases.3 This makes it difficult for patients to recover fast from attacks, and sometimes it can be life-threatening.3
- Neurological complications: Untreated symptoms can lead to permanent nerve damage, seizures and muscle weakness.4
- Psychiatric complications: The disease can cause a lot of distress among patients and may lead to anxiety or hallucinations.4
- Organ damage: The organs most at risk are the nervous system and gastrointestinal system.5
- The quality of life is deeply affected if the severe symptoms of AIP are not treated at the right time.5
How can I prevent AIP
There is no way to prevent AIP from developing because it is a genetic disease, what can be done is to adopt a lifestyle that reduces the likelihood of experiencing attacks. This is by minimizing the triggers, for example, by having a balanced diet, staying hydrated, medication management, hormone control and getting check-ups regularly.
How common is AIP
AIP affects both men and women but is more commonly found among females of reproductive age (ages between 15-50) and individuals that are of Northern European descent, with a higher prevalence among Swedish individuals.4
What can I expect if I have AIP?
If you or a person that you know has AIP, you can expect to experience any of the symptoms mentioned before and that the symptoms appear after puberty or during your 20 or 30.5 It is important to seek medical advice to avoid acute attacks and to obtain adequate treatment.
When should I see a doctor?
You should get medical advice if you experience any of the symptoms mentioned if you experience new symptoms, if you are having an acute attack or if you are trying to get pregnant.
Acute Intermittent Porphyria (AIP) is a rare metabolic disorder that consists of the deficiency of the enzyme hydroxymethylbilane synthase (HMBS). The deficiency of this enzyme can cause the accumulation of toxic heme metabolites aminolevulinic acid (ALA) and porphobilinogen (PBG) in the body. This is an autosomal dominant disease, which means that the disease can be transmitted from any of the parents to the child. The disease by itself does not produce symptoms, and some patients will never present any symptoms in their whole life. The disease usually will be triggered by external factors such as excess alcohol consumption, infections, use of specific drugs, hormonal changes or dietary changes.
The severity and frequency of the outbreaks of symptoms vary from one person to another, but if undiagnosed, the symptoms can provoke life-threatening complications. Depending on the case, the treatment may need the coordinated efforts of diverse specialists. The treatment for AIP includes the use of hematin to reduce the production of porphyrin precursors to prevent complications and suppress heme creation in the liver. AIP can mimic symptoms of other diseases so it is important to test for similar diseases to differentiate them. In case of an acute attack, the patient may need hospitalization, adequate caloric support, correction and monitoring of electrolytes, discontinuing porphytogenic agents and hemin or glucose infusions. It is important to seek medical advice if you experience any of the symptoms mentioned, if you experience new symptoms, if you are having an acute attack or if you are trying to get pregnant.
- Gonzalez-Mosquera LF, Sonthalia S. Acute intermittent porphyria. En: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 [cited 23 August 2023]. Available on: http://www.ncbi.nlm.nih.gov/books/NBK547665/
- Ramzan A, Cao JJL, Frazer JS, Stein P, Ahmad S. A case of acute intermittent porphyria leading to severe disability in a young 21-year-old female. Cureus [Internet]. 8 February 2023 [cited 23 August 2023]; Available on: https://www.cureus.com/articles/125300-a-case-of-acute-intermittent-porphyria-leading-to-severe-disability-in-a-young-21-year-old-female
- Kizilaslan EZ, Ghadge NM, Martinez A, Bass M, Winayak R, Mathew M, et al. Acute intermittent porphyria’s symptoms and management: a narrative review. Cureus [Internet]. 13 March 2023 [cited 23 August 2023]; Available on: https://www.cureus.com/articles/138850-acute-intermittent-porphyrias-symptoms-and-management-a-narrative-review