Acute Hepatic Porphyria (AHP)

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Description

Acute hepatic porphyria (AHP) is a rare group of genetic disorders affecting the liver‘s ability to break down certain molecules. This can lead to a buildup of toxic substances in the body, causing a range of symptoms that can be severe and life-threatening. AHP is often inherited, but it can also occur due to environmental factors. This blog provides a comprehensive overview of AHP, including its causes, symptoms, diagnosis, management, and ways to live a fulfilling life with the condition.

Genes Involved

AHP is caused by mutations in specific genes involved in the heme synthesis pathway. Heme is a molecule essential for the function of hemoglobin, a protein in red blood cells responsible for oxygen transport. The specific genes involved depend on the type of AHP. Here are some examples:

• Hydroxymethylbilane synthase (HMBS) gene: Mutations in this gene cause acute intermittent porphyria (AIP), the most common type of AHP.
• Porphobilinogen deaminase (PBGD) gene: Mutations in this gene cause δ-aminolevulinate dehydratase deficiency porphyria (ADP)
• Uroporphyrinogen I synthase (UROS) gene: Mutations in this gene cause congenital erythropoietic porphyria (CEP)
• Coproporphyrinogen oxidase (CPOX) gene: Mutations in this gene cause hereditary coproporphyria (HCP)

Recognizing the Signs and Symptoms

AHP symptoms can vary widely and may not always be present. Some common signs and symptoms include:

• Abdominal pain: Often severe and accompanied by nausea, vomiting, and constipation
• Neurological symptoms: Confusion, seizures, paralysis, and mental changes
• Skin abnormalities: Increased sensitivity to sunlight, dark urine, and reddish-brown discoloration of the skin
• Elevated liver enzymes: Indicating liver damage
• Other symptoms: High blood pressure, rapid heartbeat, and breathing difficulties

Symptoms may appear suddenly and intensify over a few days. In some cases, AHP can cause a life-threatening crisis. It‘s important to seek medical attention immediately if you experience any of these symptoms.

Causes

AHP is primarily caused by genetic mutations inherited from parents. It can also occur due to environmental factors that trigger symptoms in individuals with a genetic predisposition.

• Genetic mutations: Most cases of AHP are inherited in an autosomal dominant pattern, meaning a person only needs to inherit one copy of the mutated gene from a parent to develop the disorder.
• Environmental triggers: Certain factors can trigger AHP symptoms in individuals with a genetic predisposition. These triggers include:
  • Certain medications: Barbiturates, sulfonamides, and some antibiotics
  • Alcohol consumption: Excessive alcohol intake can worsen symptoms
  • Hormonal fluctuations: Menstrual cycles, pregnancy, and menopause can trigger attacks
  • Dietary factors: Low-carbohydrate diets and fasting
  • Stress: Physical or emotional stress can trigger symptoms

Inheritance/recurrence risk

AHP is typically inherited in an autosomal dominant pattern. This means a person has a 50% chance of inheriting the mutated gene from a parent with AHP. If a person inherits the mutated gene, they will likely develop AHP at some point in their life. However, the severity and frequency of symptoms can vary widely.

There is no cure for AHP, but with proper management, individuals can live relatively normal lives. Genetic testing can be used to determine if a person is a carrier of the mutated gene or if they have the disorder.