Summary about Disease
Acute Intermittent Porphyria (AIP) is a rare genetic disorder affecting the body's production of heme, a component of hemoglobin. It primarily affects the nervous system and can cause acute attacks of abdominal pain, neurological problems, and psychiatric disturbances. AIP is caused by a deficiency in the enzyme hydroxymethylbilane synthase (also known as porphobilinogen deaminase).
Symptoms
Symptoms of AIP can vary widely among individuals, and some individuals with the genetic mutation may never experience symptoms. Acute attacks can manifest with:
Severe abdominal pain
Nausea and vomiting
Constipation or diarrhea
Muscle weakness
Seizures
Mental status changes (confusion, hallucinations, anxiety, depression)
Rapid heart rate
High blood pressure
Red or brown urine
Causes
AIP is caused by a mutation in the HMBS gene, which provides instructions for making the hydroxymethylbilane synthase (HMBS) enzyme (also known as porphobilinogen deaminase). This enzyme is crucial for heme production. A deficiency in HMBS leads to a buildup of porphyrin precursors (such as porphobilinogen and aminolevulinic acid), which can be toxic to the nervous system. The condition is inherited in an autosomal dominant manner, meaning that only one copy of the mutated gene is necessary to cause the disorder.
Medicine Used
Treatment for AIP focuses on managing acute attacks and preventing future episodes. Medications include:
Hemin (Panhematin or Normosang): This is the primary treatment for acute attacks. It helps to reduce the production of porphyrin precursors.
Glucose: Intravenous glucose can help to suppress porphyrin production during an attack.
Pain relievers: Opioids may be necessary to manage severe abdominal pain.
Anti-nausea medications: To control nausea and vomiting.
Beta-blockers: To manage rapid heart rate and high blood pressure.
Givosiran (Givlaari): An RNA interference therapy to reduce porphyrin synthesis.
Other medications: Such as those to control seizures or psychiatric symptoms, are used as needed.
Is Communicable
AIP is not communicable. It is a genetic disorder, not an infectious disease.
Precautions
Individuals with AIP should take precautions to avoid factors that can trigger attacks, including:
Certain medications: Barbiturates, sulfonamide antibiotics, and some tranquilizers can trigger attacks. A doctor or pharmacist should review all medications.
Alcohol: Avoid or limit alcohol consumption.
Smoking: Avoid smoking.
Dieting or fasting: Maintain a regular, balanced diet. Avoid prolonged periods without food.
Stress: Manage stress through relaxation techniques.
Infections: Treat infections promptly.
Hormonal changes: Women may experience attacks related to their menstrual cycle. Hormonal therapies should be carefully considered with a doctor.
How long does an outbreak last?
The duration of an AIP attack can vary. Some attacks may resolve within a few days with treatment, while others can last for weeks or even months if not promptly treated. The severity and individual response to treatment influence the duration.
How is it diagnosed?
Diagnosis of AIP involves:
Clinical Evaluation: Assessment of symptoms and medical history.
Urine Testing: Elevated levels of porphyrin precursors (porphobilinogen (PBG) and aminolevulinic acid (ALA)) in the urine during an acute attack. Testing should be performed during an acute attack for best results.
Blood Testing: Elevated levels of porphyrin precursors in the blood.
Genetic Testing: HMBS gene mutation analysis to confirm the diagnosis. This is especially useful for family members of affected individuals.
Enzyme Activity Assay: Measuring HMBS enzyme activity in red blood cells.
Timeline of Symptoms
The timeline of symptoms in AIP can vary.
Onset: Symptoms often begin in adulthood, typically between the ages of 20 and 40.
Progression: Symptoms may develop gradually or suddenly, with periods of remission between attacks.
Acute Attacks: An acute attack can last from days to weeks.
Chronic Symptoms: Some individuals may experience chronic symptoms, such as persistent pain or fatigue.
Important Considerations
Early Diagnosis: Early diagnosis and treatment are crucial to prevent severe complications.
Family Screening: Family members of individuals with AIP should be screened for the genetic mutation.
Medication Avoidance: Careful avoidance of trigger medications is essential.
Dietary Management: Maintaining a regular, balanced diet is important.
Psychological Support: Individuals with AIP may benefit from psychological support to cope with the challenges of the condition.
Expert Consultation: Management of AIP should be guided by a physician with expertise in porphyrias.