Porphyria: Difference between revisions
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==Background== | ==Background== | ||
* | *Related to defect(s) in heme synthesis causing a buildup of porphyrins | ||
* Heme is a component of many essential hemoproteins, such as hemoglobin, myoglobin and cytochromes, including the cytochrome P450 enzymes | *Autosomal dominant, but poor penetrance | ||
* 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. | *Inherited and/or acquired disorders of in which there are enzyme deficiencies involved in heme biosynthesis. | ||
* The enzyme deficiencies in porphyria limit the capacity of the liver to increase heme synthesis. | *Heme is a component of many essential hemoproteins, such as hemoglobin, myoglobin and cytochromes, including the cytochrome [[P450]] enzymes | ||
* 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]] | |||
* Neurologic symptoms | ==Clinical Features== | ||
*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== | ==Differential Diagnosis== | ||
{{Abdominal Pain DDX Diffuse}} | |||
{{Extra-abdominal sources of abdominal pain DDX}} | |||
== | ==Evaluation== | ||
* | ''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 | *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== | ==Management== | ||
* | *Opioid analgesia | ||
* | *Avoid/discontinue offending medications | ||
* | **Most seizure medications contraindicated: [[Benzodiazepines]], [[gabapentin]], [[levetiracetam]], and [[vigabatrin]] okay | ||
* Treat any electrolyte abnormalities | **Avoid [[reglan]] | ||
* | *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== | ==Disposition== | ||
* Admission to a monitored bed | *Admission to a monitored bed | ||
==See Also== | ==See Also== | ||
*[[Abdominal pain]] | |||
*[[Acute intermittent porphyria]] | |||
==External Links== | ==External Links== | ||
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]] |
Revision as of 04:18, 5 April 2019
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
- Acute abdominal pain (85-90% of attacks)
- Nausea/vomiting
- Constipation and/or diarrhea
- Acute abdominal pain (85-90% of attacks)
- 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
- Abdominal aortic aneurysm
- Acute gastroenteritis
- Aortoenteric fisulta
- Appendicitis (early)
- Bowel obstruction
- Bowel perforation
- Diabetic ketoacidosis
- Gastroparesis
- Hernia
- Hypercalcemia
- Inflammatory bowel disease
- Mesenteric ischemia
- Pancreatitis
- Peritonitis
- Sickle cell crisis
- Spontaneous bacterial peritonitis
- Volvulus
Extra-abdominal Sources of Abdominal pain
- MI
- Aortic Dissection
- PNA
- PE
- Testicular Torsion
- Herpes Zoster
- Muscle spasm
- Spinal pathology
- Strep Pharyngitis (peds)
- Mononucleosis
- DKA
- ETOH Ketoacidosis
- Uremia
- Sickle Cell Crisis
- SLE
- Vasculitis
- Glaucoma
- Hyperthyroidism
- Methanol Poisoning
- Heavy Metal toxicity
- Addison's disease
- Porphyria
- Paroxysmal nocturnal hemoglobinuria
- Black widow spider bite
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
- Most seizure medications contraindicated: Benzodiazepines, gabapentin, levetiracetam, and vigabatrin okay
- Avoid reglan
- 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
- 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