Porphyria: Difference between revisions

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* 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
 
==Clinical Features==
==Clinical Features==
*Potential clues to a diagnosis of porphyria include use of potentially porphyrinogenic drugs such as sulfonamides, barbiturates, rifampin or metoclopramide, and premenstrual symptoms in women.
*Potential clues to a diagnosis of porphyria include use of potentially porphyrinogenic drugs such as sulfonamides, barbiturates, rifampin or metoclopramide, and premenstrual symptoms in women.

Revision as of 14:39, 11 January 2016

Background

  • Porphyrias are 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

  • Potential clues to a diagnosis of porphyria include use of potentially porphyrinogenic drugs such as sulfonamides, barbiturates, rifampin or metoclopramide, and premenstrual symptoms in women.
  • Gastrointestinal symptoms: Acute abdominal pain occurs in about 85-90% of attacks and is neurologic in origin. It can be associated with nausea, vomiting, constipation and/or diarrhea.
  • Neurologic symptoms: Diffuse MSK pain and headache are common. Objective sensory loss may be found in up to 40% of cases. Peripheral motor neuropathy is an indication of a severe and potentially life-threatening attack. Neuropathy can progress to respiratory failure in hours or days. Sudden death, presumably from cardiac arrhythmia may occur. Bladder paresis may cause dysuria and hesitancy. CNS effects include presentations with agitation, confusion, combativeness and other acute neuropsychiatric, as well as seizure/coma/death.

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

External Links

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