Porphyria, acute intermittent

Acute Intermittent Porphyria
Synonyms	N/A
Pronounce	N/A
Specialty	N/A
Symptoms	Abdominal pain, vomiting, neuropathy, seizures
Complications	N/A
Onset	Typically after puberty
Duration	Episodic
Types	N/A
Causes	Genetic mutation in HMBS gene
Risks	Family history, certain drugs, alcohol, fasting
Diagnosis	Urine tests, genetic testing
Differential diagnosis	N/A
Prevention	N/A
Treatment	Avoidance of triggers, glucose, hemin
Medication	N/A
Prognosis	Variable
Frequency	N/A
Deaths	N/A

Acute Intermittent Porphyria (AIP) is a rare metabolic disorder that affects the production of heme, an essential component of hemoglobin. It is one of the porphyrias, a group of disorders caused by abnormalities in the chemical steps leading to heme production. AIP is characterized by a deficiency of the enzyme hydroxymethylbilane synthase (HMBS), also known as porphobilinogen deaminase.

Pathophysiology

AIP is caused by a partial deficiency of the enzyme hydroxymethylbilane synthase (HMBS), which is the third enzyme in the heme biosynthetic pathway. This deficiency leads to the accumulation of porphyrin precursors, particularly porphobilinogen (PBG) and aminolevulinic acid (ALA), in the body. These precursors are neurotoxic and are responsible for the clinical manifestations of the disease.

Genetics

AIP is an autosomal dominant disorder, meaning that a single copy of the mutated gene can cause the disease. The gene responsible for AIP is the HMBS gene, located on chromosome 11q23.3. Mutations in this gene lead to reduced activity of the HMBS enzyme.

Clinical Presentation

The symptoms of AIP are often episodic and can be triggered by various factors such as certain medications, alcohol, fasting, and stress. The most common symptoms include:

• Severe abdominal pain
• Vomiting
• Neuropathy, which may manifest as muscle weakness or paralysis
• Seizures
• Hypertension
• Tachycardia

Diagnosis

The diagnosis of AIP is based on clinical suspicion and confirmed by laboratory tests. The following tests are commonly used:

• Urine tests for elevated levels of porphobilinogen (PBG) and aminolevulinic acid (ALA)
• Genetic testing to identify mutations in the HMBS gene

Management

Management of AIP involves both acute treatment of attacks and long-term prevention of future episodes. Key strategies include:

• Avoidance of known triggers such as certain drugs, alcohol, and fasting
• Administration of glucose or carbohydrate loading to suppress heme synthesis
• Intravenous hemin to reduce the production of porphyrin precursors

Prognosis

The prognosis of AIP varies depending on the frequency and severity of attacks. With proper management, many individuals can lead normal lives. However, recurrent attacks can lead to chronic complications such as chronic pain and neuropathy.

See Also

• Porphyria
• Heme
• Hemoglobin

External Links

• [American Porphyria Foundation](https://www.porphyriafoundation.com)
• [National Organization for Rare Disorders](https://rarediseases.org)