Acute Intermittent Porphyria - Clinicals, Diagnosis, and Management

Endocrinology, Metabolism and Nutrition

Clinicals - History

Fact Explanation
Classic triad of symptoms during acute exacerbations A triad of symptoms, abdominal pain, psychiatric symptoms (hysteria, hallucinations, paranoia) and pheripheral neuropathy occurs. Abdominal pain is usually colicky and severe, mostly involves the epigastrium and lasts for several days. Nausea and vomiting may also be present. Classic triad of symptoms during acute exacerbations
A triad of symptoms, abdominal pain, psychiatric symptoms (hysteria, hallucinations, paranoia) and pheripheral neuropathy occurs. Abdominal pain is usually colicky and severe, mostly involves the epigastrium and lasts for several days. Nausea and vomiting may also be present.
Constipation or diarrhea Due to autonomic disturbances. Constipation or diarrhea
Due to autonomic disturbances.
Neuropathies Peripheral, motor neuropathies are commoner than sensory neuropathy. Symptoms include constipation , colicky abdominal pain and vomiting. Hypertension restlessness, tremor and increased sweating occurs secondary to autonomic neuropathy. Painful neuropathies occur especially in the upper body. Neuropathies
Peripheral, motor neuropathies are commoner than sensory neuropathy. Symptoms include constipation , colicky abdominal pain and vomiting. Hypertension restlessness, tremor and increased sweating occurs secondary to autonomic neuropathy. Painful neuropathies occur especially in the upper body.
Central nervous system disturbances Cortical blindness, seizures, delirium, coma, insomnia and depression. Seizures and coma may arise secondary to hyponatremia. Central nervous system disturbances
Cortical blindness, seizures, delirium, coma, insomnia and depression. Seizures and coma may arise secondary to hyponatremia.
Symptoms of bladder dysfunction Patients may complain of urinary retention, incontinence, and dysuria. Symptoms of bladder dysfunction
Patients may complain of urinary retention, incontinence, and dysuria.
History of exposure to a precipitant Usually this autosomal dominant disease does not manifest until second or third decade of life, because some activity of the enzyme (porphobilinogen deaminase) remains. Some precipitants may cause exacerbations and also may cause early presentation. Common precipitants are fasting, dehydration, stress and infection. Physiological hormonal fluctuations (menstruation and pregnancy) may also act as a precipitant. Barbiturates and steroids are common precipitant drugs. History of exposure to a precipitant
Usually this autosomal dominant disease does not manifest until second or third decade of life, because some activity of the enzyme (porphobilinogen deaminase) remains. Some precipitants may cause exacerbations and also may cause early presentation. Common precipitants are fasting, dehydration, stress and infection. Physiological hormonal fluctuations (menstruation and pregnancy) may also act as a precipitant. Barbiturates and steroids are common precipitant drugs.
Symptoms of chronic kidney disease Patients develop chronic kidney disease secondary to long standing hypertension. Symptoms of chronic kidney disease
Patients develop chronic kidney disease secondary to long standing hypertension.
Neuropsychiatric symptoms May be the only presenting complaint in some patients. Can cause psychosis, anxiety, depression, agitation and delirium. Neuropsychiatric symptoms
May be the only presenting complaint in some patients. Can cause psychosis, anxiety, depression, agitation and delirium.

Clinicals - Examination

Fact Explanation
Pulse Tachycardia or bradycardia and arrhythmias occur due to autonomic neuropathy. Pulse
Tachycardia or bradycardia and arrhythmias occur due to autonomic neuropathy.
Blood pressure Hypotension or hypertension can occur secondary to autonomic neuropathy. Blood pressure
Hypotension or hypertension can occur secondary to autonomic neuropathy.
Motor neuropathy Mostly lower limb muscle groups are paralyzed. Patients can have quadriparesis as well. Lower motor type paralysis is seen. (The muscle tone, power and reflexes are either absent or diminished, the extensor plantar response is absent) Motor neuropathy
Mostly lower limb muscle groups are paralyzed. Patients can have quadriparesis as well. Lower motor type paralysis is seen. (The muscle tone, power and reflexes are either absent or diminished, the extensor plantar response is absent)
Respiratory rate Bulbar paralysis may cause respiratory depression. Respiratory rate
Bulbar paralysis may cause respiratory depression.
Abdominal examination Often normal. Abdominal examination
Often normal.
Mental status examination May show disturbances in mental status. Mental status examination
May show disturbances in mental status.

Investigations - Diagnosis

Fact Explanation
Urinary porphobilinogen (PBG) and δ‐aminolaevulinic acid Levels are increased especially during acute attacks. Urinary porphobilinogen (PBG) and δ‐aminolaevulinic acid
Levels are increased especially during acute attacks.
Serum porphobilinogen Increased levels are observed during acute attacks. Serum porphobilinogen
Increased levels are observed during acute attacks.
Stool porphyrins May be normal or increased. Stool porphyrins
May be normal or increased.
Genetic testing Diagnose the genetic defects responsible for enzyme deficiency. Genetic testing
Diagnose the genetic defects responsible for enzyme deficiency.

Investigations - Management

Fact Explanation
Serum electrolytes Hyponatremia can present as a result of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). It is non-specific and not diagnostic. Serum electrolytes
Hyponatremia can present as a result of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). It is non-specific and not diagnostic.
Electrocardiogram Evaluates arrhythmia. Electrocardiogram
Evaluates arrhythmia.
Arterial blood gas analysis Detects acid base disturbances secondary to respiratory depression. Arterial blood gas analysis
Detects acid base disturbances secondary to respiratory depression.
Urinary Porphobilinogen Using Watson and Schwartz test this enables screening of patients to diagnose an acute attack. Urinary Porphobilinogen
Using Watson and Schwartz test this enables screening of patients to diagnose an acute attack.

Management - Supportive

Fact Explanation
Analgesics Pain control usually requires narcotics. Analgesics
Pain control usually requires narcotics.
Laxatives and stool softeners Treat constipation which results secondary to narcotic analgesics and autonomic neuropathy. Laxatives and stool softeners
Treat constipation which results secondary to narcotic analgesics and autonomic neuropathy.
Anti- epileptics Controls seizures. Anti- epileptics
Controls seizures.
Sedatives Propofol and anti-epileptics are widely used. This will reduce the anxiety. Sedatives
Propofol and anti-epileptics are widely used. This will reduce the anxiety.
Fluid management Patients often have dehydration. Fluid management
Patients often have dehydration.
Electrolyte Electrolyte disturbances should be corrected. Electrolyte
Electrolyte disturbances should be corrected.
Antihypertensive Some patients remain hypertensive. Antihypertensive medication should be started to control blood pressure. Antihypertensive
Some patients remain hypertensive. Antihypertensive medication should be started to control blood pressure.
Treatment of chronic kidney disease Chronic kidney disease and the hypertensive complications are the most common cause of death. Treatment of chronic kidney disease
Chronic kidney disease and the hypertensive complications are the most common cause of death.
Intubation and mechanical ventilation Patients with respiratory failure should be ventilated. Intubation and mechanical ventilation
Patients with respiratory failure should be ventilated.
Health education Patients should be advised to avoid precipitants. Health education
Patients should be advised to avoid precipitants.

Management - Specific

Fact Explanation
High doses of glucose (300-500 gm/day) In mild disease this can inhibit heme synthesis which in turn reduces the synthesis of porphyrin precursors. High doses of glucose (300-500 gm/day)
In mild disease this can inhibit heme synthesis which in turn reduces the synthesis of porphyrin precursors.
Hematin (4 mg/kg/d for 4 days) This is the preferred mode of treatment in severe attacks with neurological symptoms. Hematin (4 mg/kg/d for 4 days)
This is the preferred mode of treatment in severe attacks with neurological symptoms.

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  1. CHURCH SE, MCCOLL KE, MOORE MR, YOUNGS GR. Hypertension and renal impairment as complications of acute porphyria. Nephrol Dialysis Transplant [online] 1992; 7: 986–90. [viewed 18 April 2014] Available from: http://ndt.oxfordjournals.org/content/7/10/986.abstract?ijkey=4a3208b1b2c20d6e621b71a216b615a7c028a6a9&keytype2=tf_ipsecsha
  2. DISLER PB, MOORE MR. Drug therapy in the acute porphyrias. Clin Dermatol [online] 1985; 3: 112–24 [viewed 18 April 2014] Available from: http://dx.doi.org/10.1016/0738-081X(85)90037-9
  3. ELDER GH, HIFT RJ, MEISSNER PN. The acute porphyrias. Lancet [online] 1997; 349: 1613–17 [viewed 18 April 2014] Available from: doi:10.1016/S0140-6736(96)09070-8
  4. ELLENCWEIG N, SCHOENFELD N, ZEMISHLANY Z. Acute intermittent porphyria: psychosis as the only clinical manifestation. Isr J Psychiatry Relat Sci.[Online] 2006;43(1):52-6. [Viewed 18 April 2014]. Available from: http://doctorsonly.co.il/wp-content/uploads/2011/12/2006_1_10.pdf
  5. HENRY T, VIKRAM P. K., PASHTOON M. K. Clinical Manifestations and Diagnostic Challenges in Acute Porphyrias. Case Reports in Hematology [online] 2013: 2013 [viewed 18 April 2014] Available from: http://dx.doi.org/10.1155/2013/628602
  6. JAMES M. F. M., HIFT R. J. Porphyrias. Br J Anaesth [online] 2000; 85: 143–53. [viewed 18 April 2014] Available from: http://bja.oxfordjournals.org/content/85/1/143.full
  7. LAIWAH AC, MACPHEE GJ, BOYLE P, MOORE MR, GOLDBERG A. Autonomic neuropathy in acute intermittent porphyria. J Neurol Neurosurg Psychiatry. [online] 1985;48:1025–30. [viewed 18 April 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/4056804
  8. MADHUR M., GIRIJA P. R., HARI H. D. Intensive care management of patients with acute intermittent porphyria: Clinical report of four cases and review of literature. Indian J Crit Care Med. [online] 2010 Apr-Jun; 14(2): 88–91. [viewed 18 April 2014] Available from: doi: 10.4103/0972-5229.68222
  9. SCHUURMANS M.M., SCHNEIDER-YIN X., RÜFENACHT U.B., SCHNYDER C., MINDER C.E. Influence of Age and Gender on the Clinical Expression of Acute Intermittent Porphyria Based on Molecular Study of Porphobilinogen Deaminase Gene among Swiss Patients. Molecular Medicine [online] 2001: 7 (8) 535-542. [viewed 18 April 2014] Available from: http://www.scopus.com/record/display.url?eid=2-s2.0-0035434324&origin=inward&txGid=DC43BEC7F96195A75BC33A70F5FBBBA2.y7ESLndDIsN8cE7qwvy6w%3a2
  10. SOUMITRA G., PRANIT K.R.C., HIRANYA K. G. An analysis of six cases of acute intermittent porphyria (AIP). Indian J Psychiatry [online] 2006 Jul-Sep; 48(3): 189–192. [viewed 18 April 2014] Available from: doi: 10.4103/0019-5545.31584
  11. UNZU C., SAMPEDRO A., SARDH E. et al., “Renal failure affects the enzymatic activities of the three first steps in hepatic heme biosynthesis in the acute intermittent porphyria mouse,” PLoS One [online] 2012: 7 (3). [viewed 18 April 2014] Available from: DOI: 10.1371/journal.pone.0032978