Porphyria

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Background

  • Related to defect(s) in heme synthesis causing a buildup of porphyrins
  • Autosomal dominant, but poor penetrance
  • 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

Triggers

  • Infection, metabolic stress
  • Carbohydrate deficiency
  • Tobacco, EtOH
  • Porphyrinogenic drugs: sulfonamides, barbiturates, rifampin or metoclopramide

Clinical Features

  • Gastrointestinal symptoms
  • 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

Diffuse Abdominal pain

Extra-abdominal Sources of Abdominal pain

Evaluation

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

  • Spot urinary porphobilinogen (sendout at most hospitals)
    • Normal = 0-4mg/day
    • acute attack, spot urine can be 20-200mg/L
  • Recurrent attacks in a patient with proven acute porphyria are usually similar and can be diagnosed on clinical grounds without biochemical reconfirmation.

Management

  • Opioid analgesia
  • Avoid/discontinue offending medications
  • Treat any electrolyte abnormalities
  • beta-blockers can be used to treat tachycardia
  • Glucose load
    • Decreases porphyrin production
    • Typical protocol is D10W 3-4 liters daily x 4 days
    • Risk of hyponatremia given significant free water load
  • Hemin (Panhematin┬«)
    • Decreases porphyrin production, significantly more potent than glucose
    • Recommended for most cases requiring hospitalization, or any with neurologic symptoms
    • 3-4mg/kg IV daily x 4 days
    • Can cause significant infusion site phlebitis - minimize by reconstituting in 25% albumin; consider central venous administration
    • Very expensive - around $8000 per 313mg vial

Disposition

  • Admission to a monitored bed

See Also

External Links

http://www.porphyriafoundation.com/

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