Porphyria: Difference between revisions
 
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==Background==
==Background==
* Porphyrias are inherited and/or acquired disorders of in which there are enzyme deficiencies involved in heme biosynthesis.
[[File:Heme synthesis.png|thumb|Heme synthesis with reactions occuring in the cytoplasm and some in the mitochondrion (yellow).]]
* Heme is a component of many essential hemoproteins, such as hemoglobin, myoglobin and cytochromes, including the cytochrome P450 enzymes
*Inherited and/or acquired disorders in which there are enzyme deficiencies involved in heme biosynthesis, resulting in build up of porphyrins (Porphobilinogen and δ-Aminolevulinic acid [ALA])
* 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.  
*Heme is a component of many essential hemoproteins, such as hemoglobin, myoglobin and cytochromes, including the cytochrome [[P450]] enzymes
* The enzyme deficiencies in porphyria limit the capacity of the liver to increase heme synthesis.  
*[[Acute intermittent porphyria]] is most salient to EM
* 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  
*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==
==Clinical Features==
* 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.
[[File:Urine of patient with porphyria.png|thumb|Urine on the first day (left) compared to urine after three days of sun exposure (right) showing the classic change in color to "port wine-color."]]
*Gastrointestinal symptoms
**Acute [[abdominal pain]] (85-90% of attacks)
***[[Nausea/vomiting]]
***[[Constipation]] and/or [[diarrhea]]
*Port wine-colored urine
*Diffuse musculoskeletal pain
*Neurologic symptoms
**[[Headache]]
**[[Seizure]]
**[[Numbness|Sensory loss]] (40%)
***An indication of a severe and potentially life-threatening attack
***Neuropathy can progress to [[respiratory failure]] in hours or days
**[[Urinary retention|Bladder paresis]]
*Psychiatric symptoms
**Increased risk of schizophrenia and bipolar disorder <ref>Fredrick, Thomas, M. D., et al. “Turning Purple with Pain.” The New England Journal of Medicine, vol. 385, no. 6, 2021, pp. 549–54, doi:10.1056/NEJMcps2105278.</ref>
**[[Agitation]], [[confusion]], combativeness
**Anxiety & depression (55%)<ref>Fredrick, Thomas, M. D., et al. “Turning Purple with Pain.” The New England Journal of Medicine, vol. 385, no. 6, 2021, pp. 549–54, doi:10.1056/NEJMcps2105278.</ref>


* 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==
{{Abdominal Pain DDX Diffuse}}


==Differential Diagnosis==
{{Extra-abdominal sources of abdominal pain DDX}}
* Consider porphyria in patients with abdominal pain that is unexplained after an initial workup has excluded common causes (appendicitis, cholecystitis, pancreatitis, etc).


==Diagnosis==
==Evaluation==
* Measuring urinary porphobilinogen is most important for diagnosis of acute porphyrias. Porphobilinogen (PBG) excretion is normally 0-4 mg/day, and is approximately in the same range when expressed as mg/g creatinine or even as mg/L. In an acute attack, spot urine porphobilinogen (PBG) levels are substantially increased (20-200 mg/L).
''Consider porphyria in patients with abdominal pain that is unexplained after an initial workup has excluded common causes (appendicitis, cholecystitis, pancreatitis, etc).''
* Recurrent attacks in a patient with proven acute porphyria are usually similar and can be diagnosed on clinical grounds, and without biochemical reconfirmation.  
*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.
*[[Hyponatremia]] has been documented in up to 60% of acute attacks & is attributed to elevated levels of antidiuretic hormone<ref>Bassett AS, McDonald-McGinn DM, Devriendt K, et al. Practical guidelines for managing patients with 22q11.2 deletion syndrome. J Pediatr. 2011;159(2):332-9.e1. doi:10.1016/j.jpeds.2011.02.039</ref>


==Management==
==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 ALAS. 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.
*[[Opioid]] analgesia
* Glucose loading has a similar effect, but is much less potent and effective and should be used only for mild attacks.
*Avoid/discontinue offending medications
**Most seizure medications are contraindicated
**Acceptable [[AEDs]] include: [[benzodiazepines]], [[gabapentin]], [[levetiracetam]], and vigabatrin
**Avoid [[Reglan]]
*Treat any [[electrolyte abnormalities]]
*[[Beta-blockers]] can be used to treat [[tachycardia]]
===Decrease heme synthesis===
*[[Dextrose|Glucose]] load
**Decreases porphyrin production
**E.g. D5NS at 2L/24h<ref>https://emedicine.medscape.com/article/205220-treatment</ref>==
**Avoid D5/D10W due to 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==
==Disposition==
*Admission to a monitored bed


==See Also==
==See Also==
*[[Abdominal pain]]
*[[Acute intermittent porphyria]]


==External Links==
==External Links==
{{#widget:YouTube|id=VQHz0Qu-OjA}}


http://www.porphyriafoundation.com/
==References==
==References==
#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.
#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
#Deacon AC, Peters TJ, Identification of acute porphyria: evaluation of a commercial screening test for urinary porphobilinogen. Ann Clin Biochem. 1998;35:726-32
<references/>
<references/>
[[Category:Heme/Onc]]

Latest revision as of 04:21, 25 April 2025

Background

Heme synthesis with reactions occuring in the cytoplasm and some in the mitochondrion (yellow).
  • Inherited and/or acquired disorders in which there are enzyme deficiencies involved in heme biosynthesis, resulting in build up of porphyrins (Porphobilinogen and δ-Aminolevulinic acid [ALA])
  • Heme is a component of many essential hemoproteins, such as hemoglobin, myoglobin and cytochromes, including the cytochrome P450 enzymes
  • Acute intermittent porphyria is most salient to EM
  • 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

Clinical Features

Urine on the first day (left) compared to urine after three days of sun exposure (right) showing the classic change in color to "port wine-color."

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.
  • Hyponatremia has been documented in up to 60% of acute attacks & is attributed to elevated levels of antidiuretic hormone[3]

Management

Decrease heme synthesis

  • Glucose load
    • Decreases porphyrin production
    • E.g. D5NS at 2L/24h[4]==
    • Avoid D5/D10W due to 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

{{#widget:YouTube|id=VQHz0Qu-OjA}}

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
  1. ↑ Fredrick, Thomas, M. D., et al. “Turning Purple with Pain.” The New England Journal of Medicine, vol. 385, no. 6, 2021, pp. 549–54, doi:10.1056/NEJMcps2105278.
  2. ↑ Fredrick, Thomas, M. D., et al. “Turning Purple with Pain.” The New England Journal of Medicine, vol. 385, no. 6, 2021, pp. 549–54, doi:10.1056/NEJMcps2105278.
  3. ↑ Bassett AS, McDonald-McGinn DM, Devriendt K, et al. Practical guidelines for managing patients with 22q11.2 deletion syndrome. J Pediatr. 2011;159(2):332-9.e1. doi:10.1016/j.jpeds.2011.02.039
  4. ↑ https://emedicine.medscape.com/article/205220-treatment
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