Acute intermittent porphyria
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Synonyms and keywords:
Overview
Acute intermittent porphyria (AIP) is a rare metabolic disorder in the production of heme, the oxygen-binding prosthetic group of hemoglobin. Specifically, it is characterized by a deficiency of the enzyme porphobilinogen deaminase.
Historical Perspective
One of the many hypothesized diagnoses of the artist Vincent van Gogh is that he and his siblings, particularly his brother Theo, suffered from AIP.[1] Another theorized sufferer was King George III of England, who even had a medallion struck to commemorate his "curing".
AIP makes an appearance on the television show House MD in season 1, episode 22 where Dr. House diagnoses his ex-wife's new husband with the disease.
It also makes an appearance on the television show Scrubs in season 4, episode 13 as a difficult to diagnose disease.
The TLC documentary drama mini-series, Mystery ER, features a landscaper with AIP who is repeatedly misdiagnosed.
Classification
AIP itself is a sub-category of diseases of broad group of disease describes as Porphyria.
Pathophysiology
AIP is autosomal dominant disease with variable penetrance and expression. It is caused by variable mutation in gene encoding porphobilinogen deaminase (PBGD) or hydroxymethylbilane synthase (HMBS) which was earlier known as uroporphyrinogen I synthase. This PBGD is present in hepatocytes as well Red Blood Cell.(RBC) It works in cytosol and converts porphobilinogen to porphobilingen deaminase. The PBGD is expressed in two forms depending on weather it is being expressed in hepatocytes or RBC. The manifestation of AIP typically occurs when production of PBGD is diminished or there is lack of expression gene encoding PBGD in hepatocytes.[2]
Causes
Drug Causes
Differentiating Acute intermittent porphyria from other Diseases
Epidemiology and Demographics
Age
Gender
Race
Risk Factors
Natural History, Complications and Prognosis
Normally, 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 porphyrin accumulates in the cytoplasm.
Diagnosis
Diagnostic Criteria
Additional factors must also be present such as hormones, drugs and dietary changes that trigger the appearance of symptoms.
Symptoms
Symptoms of AIP may include abdominal pain, constipation, and muscle weakness.
Patients who experience frequent attacks can develop chronic neuropathic pain in extremities as well as chronic pain in the gut. This is thought to be due to axonal nerve deterioration in affected areas of the nervous system. In these cases treatment with long-acting opioids may be indicated. Some cases of chronic pain can be difficult to manage and may require treatment using multiple modalities. Depression often accompanies the disease and is best dealt with by treating the offending symptoms and if needed the judicious use of anti-depressants.
Physical Examination
Urine from a person experiencing an acute attack will be red or "port wine" in color because of the presence of porphyrins. This condition is known as Porphyrinuria or Pyroluria.
Laboratory Findings
Imaging Findings
Other Diagnostic Studies
Treatment
Medical Therapy
A high-carbohydrate diet is typically recommended; in severe attacks, a glucose 10% infusion is recommended, which may aid in recovery. If drugs have caused the attack, discontinuing the offending substances is essential. Infection is one of the top causes of attacks and requires vigorous treatment. Pain is extremely severe and almost always requires the use of opiates to reduce it to tolerable levels. Pain should be treated early as medically possible due to its severity. Nausea can be severe; it may respond to phenothiazine drugs but is sometimes intractable. Hot water baths/showers may lessen nausea temporarily, but can present a risk of burns or falls.
Hematin and heme arginate are the drugs of choice in acute porphyria, in the United States and the United Kingdom, respectively. These drugs need to be given very early in an attack to be effective. Effectiveness varies amongst individuals. They are not curative drugs but can shorten attacks and reduce the intensity of an attack. Side effects are rare but can be serious. These heme-like substances theoretically inhibit ALA synthase and hence the accumulation of toxic precursors. In the United Kingdom, supplies of this drug are maintained at two national centers. In the United States, one company manufactures Panhematin for infusion. The American Porphyria Foundation has information regarding the quick procurement of the drug.
Patients with a history of acute porphyria are recommended to wear an alert bracelet or other identification at all times in case they develop severe symptoms: a result of which may be they cannot explain to healthcare professionals about their condition and the fact that some drugs are absolutely contraindicated. An attack of acute intermittant porphyria may be precipitated by one of the "four M's": medication, menstruation, malnutrition, maladies.
Contraindicated medications
History of acute intermittent porphyria is considered an absolute contraindication to the use of the following medications:
Seizures often accompany this disease. Most seizure medications exacerbate this condition. Treatment can be problematic: barbiturates must be avoided. Some benzodiazepines are safe, and, when used in conjunction with newer anti-seizure medications such as gabapentin offer a possible regime for seizure control.
Surgery
Prevention
See also
Template:Endocrine, nutritional and metabolic pathology
References
- ↑ Arnold, Wilfred N. Vincent van Gogh: Chemicals, Crises, and Creativity, Birkhãuser, Boston, 1992. ISBN 0-8176-3616-1.
- ↑ Grandchamp B, Picat C, Kauppinen R, Mignotte V, Peltonen L, Mustajoki P; et al. (1989). "Molecular analysis of acute intermittent porphyria in a Finnish family with normal erythrocyte porphobilinogen deaminase". Eur J Clin Invest. 19 (5): 415–8. PMID 2511016.
de:Akute intermittierende Porphyrie