acute intermittent porphyria

Acute Intermittent Porphyria (AIP) Description

Acute intermittent porphyria (AIP) is a rare genetic disorder that affects the production of heme, a vital molecule in the body. It is characterized by a deficiency of the enzyme hydroxymethylbilane synthase (HMBS), also known as porphobilinogen deaminase (PBGD).

Key Features:

• Rare Autosomal Dominant Disorder: AIP is an autosomal dominant disorder, meaning that a single copy of the mutated gene is enough to cause the condition.
• Deficiency in Heme Biosynthesis: The deficiency of HMBS enzyme leads to a buildup of toxic heme metabolites, such as aminolevulinic acid (ALA) and porphobilinogen (PBG).
• Acute Symptom Attacks: AIP is characterized by sudden, severe, and life-threatening attacks that can occur at any time.
• Neurological and Abdominal Symptoms: The most common symptoms of AIP include abdominal pain, constipation, rapid heartbeat, increased blood pressure, behavioral changes, and neurological symptoms.

Prevalence and Demographics:

• Rare Disease: AIP is a rare disease, affecting only a few people per million.
• Commonly Affects Females: The prevalence of AIP is found to commonly affect females.

Long-term Risks:

• Increased Risk of High Blood Pressure: Patients with AIP may have an increased risk of developing high blood pressure.
• Chronic Kidney Disease and Kidney Failure: There is also an increased risk of chronic kidney disease and kidney failure in patients with AIP.

References:

• [1] Acute intermittent porphyria (AIP) is one of the porphyrias, a group of hereditary diseases that involve defects in heme metabolism and result in excessive production of ALA and PBG. [4]
• [2] Symptoms include severe abdominal pain, constipation, a rapid heartbeat and increased blood pressure (tachycardia and hypertension), behavioral changes, and neurological symptoms. [3]
• [5] Acute intermittent porphyria, which causes abdominal pain and neurological symptoms, is an autosomal dominant disorder of heme biosynthesis in the liver that is caused by the accumulation of toxic heme metabolites ALA and PBG due to a deficiency in the enzyme HMBS. [15]

Note: The references provided are based on the information available within the search results context.

Diagnosing Acute Intermittent Porphyria (AIP)

Acute intermittent porphyria (AIP) is a rare genetic disorder that affects the production of heme, a vital molecule in the body. Diagnosing AIP requires a combination of clinical evaluation and laboratory tests.

Lab Tests for Diagnosis

Several lab tests are used to diagnose AIP, including:

• Porphobilinogen (PBG) measurement: This test measures the levels of PBG in urine, which is elevated in individuals with AIP. [1]
• Urine porphyrin fractionation: This test separates and measures different types of porphyrins in urine, which can help confirm a diagnosis of AIP. [6]
• Erythrocyte protoporphyrin measurements: This test measures the levels of protoporphyrin in red blood cells, which is often elevated in individuals with AIP. [7]

Confirmatory Tests

While these tests can suggest AIP, confirmatory tests are needed to confirm a diagnosis. These include:

• Plasma and stool porphyrins: Measuring the levels of porphyrins in plasma and stool can help confirm a diagnosis of AIP. [5]
• Genetic testing: Genetic testing can identify mutations in the PBGD gene that are associated with AIP. However, this test is only possible if a definitely affected family member has already had genetic testing. [8]

Biochemical Testing

All porphyria diagnoses, including AIP, are confirmed by biochemical testing. Clinical diagnoses without positive biochemical results are not considered diagnostic of AIP. [9]

Diagnostic Criteria

The diagnosis of acute intermittent porphyria is based on finding elevated PBG in urine in a random sample kept protected from light. This test is often used as an initial screening test for AIP. [3][10]

In summary, diagnosing AIP requires a combination of clinical evaluation and laboratory tests, including PBG measurement, urine porphyrin fractionation, erythrocyte protoporphyrin measurements, plasma and stool porphyrins, genetic testing, and biochemical testing.

References:

[1] Context 1 [3] Context 3 [5] Context 5 [6] Context 6 [7] Context 7 [8] Context 8 [9] Context 9 [10] Context 10

Differential Diagnosis of Acute Intermittent Porphyria (AIP)

Acute intermittent porphyria (AIP) is a rare genetic disorder that can be challenging to diagnose due to its nonspecific symptoms. When considering the differential diagnosis of AIP, several conditions should be ruled out.

Common Conditions Mimicked by AIP Attacks

• Guillain-Barré syndrome: This autoimmune disorder can cause muscle weakness, numbness, and pain, which are similar to the symptoms experienced during an AIP attack.
• Emicrania: Also known as migraines, this condition can cause severe headaches, nausea, and vomiting, which may be mistaken for an AIP attack.
• Acute psychotic episodes: In some cases, AIP attacks can manifest with psychiatric symptoms such as confusion, agitation, and hallucinations.

Other Acute Hepatic Porphyrias

AIP should also be differentiated from other acute hepatic porphyrias, including:

• Variegate porphyria: This condition is characterized by a deficiency of protoporphyrinogen oxidase (PPOX) and can cause similar symptoms to AIP.
• Hereditary coproporphyria: This rare disorder involves a deficiency of coproporphyrinogen oxidase (CPOX) and can present with symptoms similar to AIP.

Diagnostic Considerations

To accurately diagnose AIP, it is essential to consider the following:

• Family history: Clues from family history may be absent, as symptoms are not present in the majority of family members with a pathogenic variant in the HMBS gene.
• Porphyrin analysis: Urinary ALA and porphyrins, plasma and stool porphyrins should be analyzed to confirm the diagnosis.

References

• [2] Clues from the family history may be absent, because symptoms are not present in the majority of family members with a pathogenic