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Acute hepatic porphyria can often be misdiagnosed and may seem like navigating a maze of symptoms and tests before an AHP diagnosis is made.

Acute Hepatic Porphyria (AHP):

Guide your patients to a clear diagnosis

AHP often features chronic, debilitating symptoms punctuated by acute, potentially life-threatening exacerbations. They may inflict years of suffering and impaired quality of life. The symptoms of AHP can often resemble those of other more common conditions such as irritable bowel syndrome (IBS), fibromyalgia, and endometriosis, and consequently, patients afflicted with AHP are often misdiagnosed or remain undiagnosed for an average of 15 years.

Guide your patients to a clear AHP diagnosis by learning to detect the signs and symptoms below.

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Disease overview: Acute Hepatic Porphyria (AHP)

AHP is a rare, genetic disease that leads to accumulation of neurotoxic intermediates aminolevulinic acid (ALA) and porphobilinogen (PBG), which causes disease manifestations.

Acute hepatic porphyria pathophysiology
The inherited genetic defect for AHP disrupts the heme synthesis pathway which can cause an increase of ALAS1 in the liver.
In people with the genetic defect for AHP, 1 of the 8 enzymes in the pathway that creates heme is deficient. Certain triggers can impact the pathway and can cause an increase of aminolevulinic acid synthase 1 (ALAS1) in the liver.
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The increase of ALAS1 causes a build up of aminolevulinic acid (ALA) and porphobilinogen (PBG) in the body.
This increase of ALAS1 results in the buildup of neurotoxic intermediates—ALA and PBG—throughout the body.
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ALA and PBG are thought to cause acute attacks and symptoms of AHPs.
ALA and PBG are harmful to nerve cells and are thought to cause the acute attacks and chronic symptoms characteristic of AHP.
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Acute hepatic porphyria affects the autonomic, peripheral, and central nervous systems.
AHP affects the autonomic, peripheral, and central nervous systems.

Learn to detect the signs and symptoms of AHP,* which include:

92% of patients with AHP report abdominal pain

of patients with AHP
report abdominal pain

(mimics an acute abdomen but without specific localization)3,6

Signs and symptoms of acute hepatic porphyria (AHP) include severe, diffuse abdominal pain and 1 or more of the following nervous system symptoms or cutaneous symptoms: limb weakness or pain, anxiety or confusion, nausea or vomiting, skin lesions on sun-exposed areas. Signs and symptoms of acute hepatic porphyria (AHP) include severe, diffuse abdominal pain and 1 or more of the following nervous system symptoms or cutaneous symptoms: limb weakness or pain, anxiety or confusion, nausea or vomiting, skin lesions on sun-exposed areas. Signs and symptoms of acute hepatic porphyria (AHP) include severe, diffuse abdominal pain and 1 or more of the following nervous system symptoms or cutaneous symptoms: limb weakness or pain, anxiety or confusion, nausea or vomiting, skin lesions on sun-exposed areas.
 

32% of patients with AHP report hyponatraemia9

*AHP is comprised of four subtypes. Over 80% of cases are acute intermittent porphyria (AIP), followed by hereditary coproporphyria (HCP), variegate porphyria (VP), and the extremely rare ALA dehydratase-deficiency porphyria (ADP).

Cutaneous symptoms occur only in HCP and VP.

Nonspecific symptoms can lead to misdiagnoses

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Irritable bowel syndrome

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Endometriosis

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Fibromyalgia

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Psychiatric disorder

 
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AHP

You can diagnose AHP by sending urine (preferably early morning) protected from light to a specialised laboratory

Provide the laboratory with clinical details about the patient, the laboratory will perform the appropriate test.

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PBG

(porphobilinogen)

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Porphyrins§

 
 

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ALA

(delta-aminolevulinic acid)

PBG and ALA are porphyrin precursors that occur naturally in the heme biosynthesis pathway in the liver but reach neurotoxic levels in patients with symptomatic AHP.

§Porphyrin analyses may differentiate the specific AHP.

Where to test for AHP

Urine PBG and Porphyrins are available through the NHS via your local biochemistry department. Specialized Porphyrin Laboratories in London and Cardiff can provide advice and testing if required.

Cardiff Porphyria Service

Department of Medical Biochemistry & Immunology, University Hospital of Wales, Heath Park, Cardiff, CF14 4XW

Telephone Number:
Porphyrin laboratory: 029 2074 3565

Email: porphyria@wales.nhs.uk

King's College Hospital Porphyria Service

Porphyrin Section, Reference Biochemistry, Department of Clinical Biochemistry, Viapath
King's College Hospital, London, SE5 9RS

Telephone Number:
Porphyrin laboratory: 020 3299 3856

Email: kch-tr.porphyriaclinic@nhs.net

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References

  1. Bissell DM, Anderson KE, Bonkovsky HL. Porphyria. N Engl J Med. 2017;377(9):862-872.
  2. Bissell DM, Wang B. Acute Hepatic Porphyria. J Clin Transl Hepatol. 2015;3(1):17-26.
  3. Anderson KE, Bloomer JR, Bonkovsky HL, et al. Recommendations for the diagnosis and treatment of the acute porphyrias. Ann Intern Med. 2005;142(6):439-450.
  4. Balwani M, Wang B, Anderson KE, et al; for the Porphyrias Consortium of the Rare Diseases Clinical Research Network. Acute hepatic porphyrias: recommendations for evaluation and long-term management. Hepatology. 2017;66(4):1314-1322.
  5. Simon A, Pompilus F, Querbes W, et al. Patient Perspective on Acute Intermittent Porphyria with Frequent Attacks: A Disease with Intermittent and Chronic Manifestations. Patient. [published online June 19, 2018]. doi: 10.1007/s40271-018-0319-3.
  6. Gouya L, Bloomer JR, Balwani M, et al. EXPLORE: a prospective, multinational, natural history study of patients with acute hepatic porphyrias (AHP) with recurrent attacks. Presented at: 2017 International Congress on Porphyrins and Porphyrias; June 26, 2017; Bordeaux, France.
  7. Alfadhel M, Saleh N, Alenazi H, Baffoe-Bonnie H. Acute intermittent porphyria caused by novel mutation in HMBS gene, misdiagnosed as cholecystitis. Neuropsychiatr Dis Treat. 2014;10:2135-2137.
  8. Kondo M, Yano Y, Shirataka M, Urata G, Sassa S. Porphyrias in Japan: compilation of all cases reported through 2002. Int J Hematol. 2004;79(5):448-456.
  9. Ventura P, Cappellini MD, Biolcati G, Guida CC, Rocchi E; Gruppo Italiano Porfiria (GrIP). A challenging diagnosis for potential fatal diseases: Recommendations for diagnosing acute porphyrias. Eur J Intern Med. 25(6):497-505.
  10. Woolf J, Marsden JT, Degg T, Whatley S, Reed P, Brazil N, Stewart MF, Badminton M. Best practice guidelines on first-line laboratory testing for porphyria. Annals of Clinical Biochemistry 2017;54(2):188–198.