Acute intermittent porphyria

The clinical presentation of AIP is highly variable and non-specific. The patients are typically asymptomatic, with most gene carriers having no family history because the condition had remained latent for several generations. The syndrome marked by acute attacks affects only 10% of gene carriers.[4] The mean age at diagnosis is 33 years old.[5] Like other porphyrias, AIP is more likely to present in women.[6] A distinguishing feature of AIP that separates it from other porphyrias is the absence of photosensitive cutaneous symptoms that occur in addition to acute attacks.[7]

Porphyrias are caused by mutations in genes that encode enzymes in heme synthesis. In normal physiology, heme synthesis begins in the mitochondrion, proceeds into the cytoplasm, and finishes back in the mitochondrion. Heme is produced in all cells, but 80% of all heme is produced in erythropoietic cells in bone marrow and 15% in parenchymal cells in the liver, where turnover of hemoproteins is high. In AIP, over 100 mutations have been identified on the long arm of chromosome 11 at the HMBS gene, which codes for the cytoplasmic enzyme porphobilinogen deaminase.[21] This deficiency prevents heme synthesis, which can not be completed and the metabolite porphobilinogen accumulates in the cytoplasm.[22]

AIP is an autosomal dominant porphyria resulting in about 50% normal activity of the affected enzyme.[23] The penetrance of AIP is incomplete with only 10% of gene carriers experiencing acute attacks suggesting role for other modifying genes or environment.[24][25][26]

The exact mechanism of acute attacks is not clear. The most favored hypothesis is that porpholobilinogen buildup causes a toxic effects on neurons. The autonomic and peripheral nervous system are more vulnerable than the central nervous system because they are not protected by the blood-brain barrier.[27] This explains findings such as abdominal pain and tachycardia. Some individuals may be more likely to develop paresis based on increased susceptibility of neurons to toxins.[28]

The initial diagnosis of acute porphyria is confirmed by urinalysis, including the common method, the Watson-Schwartz test. Elevated urine porphobilinogen confirms diagnosis of AIP, hereditary coproporphyria (HCP), or variegate porphyria (VP). A positive test should be indicated with an increase of five times normal, not just a slight increase which can occur with dehydration. To distinguish between AIP from HCP and VP, fecal porphyrin levels are normal in AIP but elevated in HCP and VP.

Rapid, accurate diagnosis is important. Delays in diagnosis may result in permanent neurological damage or death.

If drugs have caused the attack, discontinuing the offending substances is essential. A high-carbohydrate (10% glucose) infusion is recommended, which may aid in recovery.

Hemin(Hematin)

Hematin and heme arginate is the treatment of choice during an acute attack. Heme is not a curative treatment, but can shorten attacks and reduce the intensity of an attack. Side-effects are rare but can be serious. Pain is extremely severe and almost always requires the use of opiates to reduce it to tolerable levels. Pain should be treated as 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.[29]

Seizures often accompany this disease. Most seizure medications exacerbate this condition due to their induction of cytochrome P450. Treatment can be problematic: Barbiturates and primidone must be avoided as they commonly precipitate symptoms.[30] Some benzodiazepines are safe, and, when used in conjunction with newer anti-seizure medications such as gabapentin, offer a possible regimen for seizure control.

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 and syphilis.[31] Another theorized sufferer was King George III of the United Kingdom[32] who even had a medallion struck to commemorate his "curing". His descendant Prince William of Gloucester was reliably diagnosed with variegate porphyria in 1968.[33] It is probable that the philosopher Jean-Jacques Rousseau suffered from porphyria.[34][35][36][37] It has even been suggested that Vlad III, Prince of Wallachia, more commonly known by his surname Dracula, suffered from porphyria.