Porphyrias

  • Diagnosis
  • Algorithms
  • Monitoring
  • Background
  • Lab Tests
  • References
  • Related Content

Indications for Testing

  • Patient with abdominal symptoms and/or cutaneous symptoms compatible with porphyria

Laboratory Testing

Differential Diagnosis

Porphyrias Testing Algorithm

  • Acute porphyrias – use urine porphobilinogen (PBG) to assess metabolic response to IV hematin
  • Porphyria cutanea tarda (PCT) – use porphyrins, total, plasma or serum, for monitoring

Porphyrias are a group of inherited or acquired enzyme disorders of the heme biosynthetic pathway that result in overproduction of porphyrins or porphyrin precursor compounds.

Epidemiology

  • Prevalence
    • Porphyria cutanea tarda (PCT) – 1/10,000
    • Acute intermittent porphyria (AIP) – 1-2/20,000
    • Variegate porphyria (VP) – 3/1,000 in Caucasians
      • Less common in other populations
    • Erythropoietic protoporphyria (EPP) – 2-5/1,000,000
    • Hereditary coproporphyria (HCP) – ≤2/1,000,000
    • Congenital erythropoietic porphyria (CEP) – ≤1/1,000,000
    • Aminolevulinic acid dehydratase deficiency porphyria (ADP) – <10 cases reported
  • Age – varies according to porphyria
    • Adults
      • PCT – manifests after 30s
      • AIP – rarely occurs before puberty; usually occurs in 30s
    • Children
      • EPP – most common childhood porphyria
      • CEP – manifests soon after birth, occasionally later
        • Late onset CEP has been documented in older adults

Classification

  • Rare disorders – all forms of porphyria together afflict fewer than 200,000 people in the U.S.
  • Classification
    • Acute
      • Neurologic symptoms
        • AIP
        • ADP
      • Neurologic and cutaneous symptoms
        • VP
        • HCP
    • Nonacute
      • PCT
      • EPP
      • CEP

Clinical Features

Risk Factors

  • Genetics – predominantly transmitted as autosomal dominant disorders
    • ADP and CEP have autosomal recessive transmission
  • PCT – associated with the following

Pathophysiology

  • Heterogenous group of inherited or acquired disorders of heme biosynthesis
    • Partial deficiency of one of seven enzymes in the pathway causes the clinical features of porphyria
    • Defined by accumulation and excretion of heme precursors specific for the individual disease

Clinical Presentation

Treatment

Indications for Laboratory Testing

Tests generally appear in the order most useful for common clinical situations.
Click on number for test-specific information in the ARUP Laboratory Test Directory

Porphobilinogen (PBG), Urine 0080260
Method: Quantitative Ion Exchange Chromatography/Spectrophotometry

Limitations

24-hour specimen is more sensitive

Follow Up

If result is negative but high clinical suspicion exists, repeat when symptoms are present

Porphyrins, Fractionation and Quantitation, Urine 2002058
Method: Quantitative High Performance Liquid Chromatography

Limitations

24-hour specimen is more sensitive

Urine coproporphyrin is elevated in many common disorders

Follow Up

If test is negative but high clinical suspicion still exists, repeat when symptoms are present 

Porphyrins and Porphobilinogen (PBG), Urine 2002181
Method: High Performance Liquid Chromatography/Ion Exchange Chromatography/Quantitative Spectrophotometry

Limitations

24-hour specimen is more sensitive

Porphyrins, Fecal 0099824
Method: Quantitative High Performance Liquid Chromatography

Limitations

Bacterial modification of fecal porphyrins is extensive

Meat in diet may influence test results

Porphyrins, Total, Plasma or Serum 0080429
Method: Quantitative Fluorometry

Limitations

Does not identify specific porphyrin

Porphobilinogen (PBG) Deaminase, Erythrocyte 0099550
Method: Quantitative Enzymatic/Fluorometry

Limitations

Not recommended for diagnosis of an individual patient

Best performed in association with a specimen from an unaffected family member

Erythrocyte Porphyrin (EP), Whole Blood 0020610
Method: Fluorometry

Limitations

Also elevated in early and late iron deficiency, anemia of chronic disease, and chronic lead poisoning

Follow Up

If lead poisoning suspected, order whole blood lead testing

Aminolevulinic Acid (ALA), Urine 0080103
Method: Quantitative Ion Exchange Chromatography/Spectrophotometry

Limitations

24-hour specimen is more sensitive

Follow Up

If lead poisoning suspected, order whole blood lead testing

Aminolevulinic Acid Dehydratase (ALAD), Blood  2011012
Method: Quantitative Enzymatic/Spectrofluorometry

Cutaneous Direct Immunofluorescence, Biopsy 0092572
Method: Direct Immunofluorescence
(Direct Fluorescent Antibody Stain)

Limitations

Characteristic pattern of staining but not specific

Epithelial Skin Antibody 0090299
Method: Indirect Immunofluorescence
(Indirect Fluorescent Antibody)

Limitations

Negative in porphyria and pseudoporphyria; positive in immunobullous diseases

Additional Tests Available

Porphyrins, Total with Reflex to Porphyrins Fractionation, Plasma 2006593
Method: Qualitative Extraction/Scanning Spectrofluorometry/Quantitative High Performance Liquid Chromatography

Guidelines

Anderson K, Bloomer J, Bonkovsky H, Kushner J, Pierach C, Pimstone N, Desnick R. Recommendations for the diagnosis and treatment of the acute porphyrias. Ann Intern Med. 2005; 142(6): 439-50. PubMed

Laboratory Diagnosis - Acute Porphyrias. European Porphyria Network. [Accessed: Nov 2015]

General References

Aarsand A, Boman H, Sandberg S. Familial and sporadic porphyria cutanea tarda: characterization and diagnostic strategies. Clin Chem. 2009; 55(4): 795-803. PubMed

American Porphyria Foundation. Houston, TX [Accessed: Apr 2015]

Balwani M, Desnick R. The porphyrias: advances in diagnosis and treatment. Blood. 2012; 120(23): 4496-504. PubMed

Frank J, Poblete-Gutiérrez P. Porphyria cutanea tarda--when skin meets liver. Best Pract Res Clin Gastroenterol. 2010; 24(5): 735-45. PubMed

Maynard B, Peters M. Histologic and immunofluorescence study of cutaneous porphyrias. J Cutan Pathol. 1992; 19(1): 40-7. PubMed

Parnas M, Frank E. Clinical Laboratory News: Porphyrias. American Association for Clinical Chemistry. [Accessed: Apr 2015]

Puy H, Gouya L, Deybach J. Porphyrias. Lancet. 2010; 375(9718): 924-37. PubMed

Sarkany R. Making sense of the porphyrias. Photodermatol Photoimmunol Photomed. 2008; 24(2): 102-8. PubMed

The Porphyrias Consortium. Rare Diseases Clinical Research Network. New York, NY [Accessed: ]

Ventura P, Cappellini M, Rocchi E. The acute porphyrias: a diagnostic and therapeutic challenge in internal and emergency medicine. Intern Emerg Med. 2009; 4(4): 297-308. PubMed

Medical Reviewers

Last Update: January 2016