Porphyria

Background

• Inherited and/or acquired disorders of in which there are enzyme deficiencies involved in heme biosynthesis.
• Heme is a component of many essential hemoproteins, such as hemoglobin, myoglobin and cytochromes, including the cytochrome P450 enzymes
• The first enzyme in the heme production pathway is ALA synthase (ALAS), which controls the rate of heme synthesis in the liver. This enzyme is down-regulated by heme.
• The enzyme deficiencies in porphyria limit the capacity of the liver to increase heme synthesis.
• When drugs, hormones or other factors that induce ALAS and CYPs are given, ALA and porphobilinogen (PBG) are overproduced and accumulate, and a neurovisceral attack may develop

Clinical Features

• History of porphyrinogenic drugs: sulfonamides, barbiturates, rifampin or metoclopramide
• Gastrointestinal symptoms
  • Acute abdominal pain (85-90% of attacks)
    • Nausea/vomiting
    • Constipation and/or diarrhea
• Neurologic symptoms
  • Diffuse musculoskeletal pain
  • headache
  • Sensory loss (40%)
    • An indication of a severe and potentially life-threatening attack
    • Neuropathy can progress to respiratory failure in hours or days
  • Bladder paresis
  • Agitation, confusion, combativeness, seizure

Differential Diagnosis

• Consider porphyria in patients with abdominal pain that is unexplained after an initial workup has excluded common causes (appendicitis, cholecystitis, pancreatitis, etc).

Diagnosis

• Measuring urinary porphobilinogen is most important for diagnosis of acute porphyrias. Porphobilinogen (PBG) excretion is normally 0-4 mg/day, but In an acute attack, spot urine porphobilinogen (PBG) levels can be 20-200 mg/L.
• Recurrent attacks in a patient with proven acute porphyria are usually similar and can be diagnosed on clinical grounds, and without biochemical reconfirmation.

Management

• The most effective therapy for the acute attack is hemin (Panhematin®). This drug corrects the deficiency of regulatory heme in the liver and down-regulates ALA synthase. The standard hemin treatment course is 3-4 mg/kg by vein once daily for 4 days. If the diagnosis is confirmed, the first dose can be given in the ED.
• Glucose loading has a similar effect, but is much less potent and effective and should be used only for mild attacks.
• Discontinue any inciting drugs
• Treat any electrolyte abnormalities
• Treat pain with narcotic analgesia and nausea with phenothiazines
• beta blockers can be used to treat tachycardia
• Seizures should be treated with gabapentin, benzodiazepines and vigabatrin. Patients who have a seizure during an acute porphyria attack rarely need long term anticonvulsant therapy.

Disposition

• Admission to a monitored bed

See Also

• Acute intermittent porphyria
• Abdominal pain

References

• 1. NR Pimstone, KE. Anderson, B Freilich. (n.d.). Emergency Room Guidelines for Acute Porphyria. American Porphyria Foundation. Retrieved January 11, 2016. From http://www.porphyriafoundation.com/for-healthcare-professionals/emergency-guidelines-for-acute-porphyria#Treatment.
• 2. Anderson KE, Bloomer, JR Bonkovsky HL, Kushner JP, Pierach CA, Pimstone NR and Desnick RJ. Recommendations for the Diagnosis and Treatment of the Acute Porphyrias. Ann Intern Med 2005; 142:439-450
• 3. Deacon AC, Peters TJ, Identification of acute porphyria: evaluation of a commercial screening test for urinary porphobilinogen. Ann Clin Biochem. 1998;35:726-32