Acute intermittent porphyria:
Acute intermittent porphyria (AIP), an autosomal dominant metabolic disorder affecting the production of heme, the oxygen-binding group of hemoglobin. Acute intermittent porphyria is due to deficiency of the enzyme porphobilinogen deaminase. It is the second most common form of porphyria (porphyria cutanea tarda being the most common).
Mechanism of Acute intermittent porphyria:
Approximately 90% of cases of acute intermittent porphyria are due to a mutation that causes decreased amounts of the enzyme, and to a lesser degree by a mutation that causes decreased activity of each enzyme molecule. Under normal circumstances, heme synthesis begins in the mitochondrion, proceeds into the cytoplasm, and finishes back in the mitochondrion. However, without porphobilinogen deaminase, a necessary cytoplasmic enzyme, heme synthesis cannot finish, and the metabolite porphobilinogen accumulates in the cytoplasm.
Symptoms of Acute intermittent porphyria:
Most patients with acute intermittent porphyria are completely free of symptoms between attacks. How the porphyrin precursors lead to these symptoms is unknown.
- Acute intermittent porphyria displays neurovisceral symptoms but no skin manifestations.
- The neurovisceral symptoms consist of autonomic neuropathies (eg, constipation, colicky abdominal pain, vomiting, hypertension), peripheral neuropathy, seizures, delirium, coma, and depression.
- The abdominal pain is severe and lasts for several days. Severe abdomen pain of short ( < 1 d) duration or chronic abdominal pain is unusual.
- AIP patients may have central nervous system signs consisting of seizures, mental status changes, cortical blindness, and coma.
- Patients often experience peripheral neuropathies that are predominantly motor and can mimic Guillain-Barré syndrome. The weakness usually starts in the lower limbs and ascends, but neuropathies can be observed in any nerve distribution.
Patients may develop autonomic neuropathies, such as hypertension and tachycardia.
Patients may have very severe abdominal pain lasting several days.
- Pain of short duration (minutes) or chronic abdominal pain is not observed in AIP.
- The pain often is epigastric and colicky in nature.
- Patients often are free of pain between attacks.
- Constipation is common and can be very severe.
- Frequently, nausea and vomiting are present.
Patients can have a wide variety of psychiatric symptoms.
- Usually, patients have concurrent neurologic or abdominal symptoms.
- Depression is very common.
Treatment for Acute intermittent porphyria:
The treatment goal for acute attacks of acute intermittent porphyria is to decrease heme synthesis and reduce the production of porphyrin precursors.
- Glucose (High doses): can inhibit heme synthesis and are useful for treatment of mild attacks.
- Hematin: for people experiencing severe attacks, especially those with severe neurologic symptoms
- Narcotics: for Pain control is best achieved with.
- Laxatives and stool softeners: should be administered with the narcotics to avert exacerbating existing constipation.
- Neurontin: for treatment of seizures. Most classic antiseizure medicines can lead to acute porphyria attacks.
References for Acute Intermittent porphyria: