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Acute intermittent porphyria
Classification and external resources
Porphobilinogen
ICD-10	E80.2
ICD-9	277.1
OMIM	176000
DiseasesDB	171
eMedicine	med/1880
MeSH	D017118

Acute intermittent porphyria (AIP) is a rare autosomal dominant^[1] metabolic disorder affecting the production of heme, the oxygen-binding prosthetic group of hemoglobin. It is characterized by a deficiency of the enzyme porphobilinogen deaminase. Acute intermittent porphyria is the second most common form of porphyria.^[2]:525

Contents 1 Mechanism of disease 2 Treatment 3 Famous sufferers 4 Cultural references 5 References 6 See also

[edit] Mechanism of disease

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.^[3]

Additional factors must also be present such as hormones, drugs, and dietary changes that trigger the appearance of symptoms. Symptoms of AIP may include abdominal pain, constipation, and muscle weakness.

[edit] Treatment

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 or showers may lessen nausea temporarily, but can present a risk of burns or falls. ^[4]

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, in theory, 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 that they cannot explain to healthcare professionals about their condition and the fact that some drugs are absolutely contraindicated. An attack of acute intermittent porphyria may be precipitated by one of the "four Ms": medication, menstruation, malnutrition, maladies.

Patients that 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. Earl Campbell from University of Maryland performed the first successful clinical trial. Although results for this trial are still undergoing rigorous testing.

Seizures often accompany this disease. Most seizure medications exacerbate this condition. Treatment can be problematic: Barbiturates must be avoided as they commonly precipitate symptoms.^[5] Some benzodiazepines are safe, and, when used in conjunction with newer anti-seizure medications such as gabapentin, offer a possible regimen for seizure control.

Urine from a person experiencing an acute attack may be red or "port wine" in color because of the presence of porphyrins. In addition, urine of AIP sufferers may turn purple when exposed to ultraviolet light for a period of time.

[edit] Famous sufferers

One of the many hypothesized diagnoses of the artist Vincent van Gogh is that he and his siblings, in particular his brother Theo, suffered from AIP.^[6] Another theorized sufferer was King George III of England ^[7] who even had a medallion struck to commemorate his "curing". His great-great-great-grandson Prince William of Gloucester was reliably diagnosed with variegate porphyria in 1968. ^[8]

[edit] Cultural references

AIP makes an appearance on the television show House in the season 1 finale, wherein House diagnoses his ex-girlfriend's husband with the disease,^[9] and also again in Season 5, Episode 10, "Let Them Eat Cake."

AIP has also made a couple of appearances on the television show Scrubs in the thirteenth episode of season 4 titled "Myocardial Infarction" and in the ninth episode of season 7 in the episode titled "My Dumb Luck." ^[10]

And most recently made an appearance in the new Doc Martin Series when the new headmaster is diagnosed with AIP

[edit] References

[edit] See also

• Porphyria
• Pyroluria
• Acute intermittent porphyria at NIH's Office of Rare Diseases

v • d • e Heme metabolism disorders (E80, 277.1, 277.4) Porphyria, hepatic and erythropoietic (porphyrin) early mitochondrial: ALAD porphyria · Acute intermittent porphyria cytoplasmic: Gunther disease/congenital erythropoietic porphyria · Porphyria cutanea tarda/Hepatoerythropoietic porphyria late mitochondrial: Hereditary coproporphyria · Variegate porphyria · Erythropoietic protoporphyria Hereditary hyperbilirubinemia (bilirubin) unconjugated: Gilbert's syndrome · Crigler-Najjar syndrome · Lucey-Driscoll syndrome conjugated: Dubin-Johnson syndrome · Rotor syndrome see also porphyrin metabolism enzymes, intermediates