The onset of back and leg pain is characterized by severe pain and stiffness in back and thighs followed by loss of tendon reflexes and paralysis. Psychiatric symptoms are present, such as paranoid schizophrenia-like features but rarely psychosis and hallucinations. The acute attacks classically present with dark-red photosensitive urine (often called port-wine urine), but this is a nonspecific symptom. Physical examination often shows no abnormalities.Hyponatremia is the most common electrolyte abnormality during acute attacks, occurring in 40% of patients and presenting as SIADH. Hypomagnesemia is also common. There are no pathognomonic signs or symptoms.The most common identified triggers for acute attacks are medications, weight loss diets, and surgery. Many medications have been associated with AIP including antibiotics, hormonal contraceptives, seizure medications, anesthetics, and HIV treatment drugs. Cause
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. This deficiency prevents heme synthesis, which can not be completed and the metabolite porphobilinogen accumulates in the cytoplasm.AIP is an autosomal dominant porphyria resulting in about 50% normal activity of the affected enzyme.
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.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. Some benzodiazepines are safe, and, when used in conjunction with newer anti-seizure medications such as gabapentin, offer a possible regimen for seizure control. Society
One of the many hypothesized diagnoses of the artist Vincent van Gogh is that he and his siblings, in particular his brother Theo, had AIP and syphilis. Another theorized case was King George III of the United Kingdom who even had a medallion struck to commemorate his "curing". His descendant Prince William of Gloucester was reliably diagnosed with variegate porphyria in 1968. It is probable that the philosopher Jean-Jacques Rousseau had porphyria. It has even been suggested that Vlad III, Prince of Wallachia, more commonly known by his surname Dracula, had porphyria. References


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