Porphyria: Difference between revisions

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*Related to defect(s) in heme synthesis causing a buildup of porphyrins
*Related to defect(s) in heme synthesis causing a buildup of porphyrins
*Autosomal dominant, but poor penetrance
*Autosomal dominant, but poor penetrance
* Inherited and/or acquired disorders of in which there are enzyme deficiencies involved in heme biosynthesis.  
*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
*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 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.  
*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
*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===
===Triggers===
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==Diagnosis==
==Diagnosis==
''Consider porphyria in patients with abdominal pain that is unexplained after an initial workup has excluded common causes (appendicitis, cholecystitis, pancreatitis, etc).''
''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)
*Spot urinary porphobilinogen (sendout at most hospitals)
**Normal = 0-4 mg/day
**Normal = 0-4 mg/day
**acute attack, spot urine can be 20-200 mg/L
**acute attack, spot urine 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 without biochemical reconfirmation.
*Recurrent attacks in a patient with proven acute porphyria are usually similar and can be diagnosed on clinical grounds without biochemical reconfirmation.


==Management==
==Management==
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**Most seizure medications contraindicated: [[Benzodiazepines]], [[gabapentin]], [[levetiracetam]], and [[vigabatrin]] okay
**Most seizure medications contraindicated: [[Benzodiazepines]], [[gabapentin]], [[levetiracetam]], and [[vigabatrin]] okay
**Avoid [[reglan]]
**Avoid [[reglan]]
* Treat any [[electrolyte abnormalities]]
*Treat any [[electrolyte abnormalities]]
* [[beta-blockers]] can be used to treat tachycardia
*[[beta-blockers]] can be used to treat tachycardia
*Glucose load
*Glucose load
**Decreases porphyrin production
**Decreases porphyrin production
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==Disposition==
==Disposition==
* Admission to a monitored bed
*Admission to a monitored bed


==See Also==
==See Also==

Revision as of 17:16, 6 July 2016

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

Diagnosis

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 = 0-4 mg/day
    • acute attack, spot urine 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 without biochemical reconfirmation.

Management

  • Narcotic 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
    • 3-4 mg/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 313 mg 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
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