Test Catalog

Test ID: PEE    
Porphyrins Evaluation, Whole Blood

Useful For Suggests clinical disorders or settings where the test may be helpful

Establishing a biochemical diagnosis of erythropoietic protoporphyria and X-linked dominant protoporphyria

Testing Algorithm Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

This test is recommended for screening patients for possible erythropoietic protoporphyria and X-linked dominant protoporphyria. In addition, it can be used for evaluation of iron-deficiency anemia and chronic lead intoxication. Testing begins with total erythrocyte porphyrins. If the result is below 80 mcg/dL, it is normal and testing is complete.

 

If the total erythrocyte porphyrin value is 80 mcg/dL or above, the protoporphyrin fractionation assay will automatically be performed at an additional charge. The fractionation test results include noncomplexed (free) protoporphyrin and zinc-complexed protoporphyrin.

 

The following algorithms are available in Special Instructions:

-Porphyria (Acute) Testing Algorithm 

-Porphyria (Cutaneous) Testing Algorithm 

 

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

The porphyrias are a group of inherited disorders resulting from enzyme defects in the heme biosynthetic pathway. Depending on the specific enzyme involved, various porphyrins and their precursors accumulate in different specimen types. The patterns of porphyrin accumulation in erythrocytes and plasma and excretion of the heme precursors in urine and feces allow for the detection and differentiation of the porphyrias.

 

Testing erythrocyte porphyrin level is most informative for patients with a clinical suspicion of erythropoietic protoporphyria (EPP) or X-linked dominant protoporphyria (XLDPP). Clinical presentation of EPP and XLDPP is identical, with onset of symptoms typically occurring in childhood. Cutaneous photosensitivity in sun-exposed areas of the skin generally worsens in the spring and summer months. Common symptoms may include itching, edema, erythema, stinging or burning sensations, and occasionally scarring of the skin in sun-exposed areas. Although genetic in nature, environmental factors can exacerbate symptoms, significantly impacting the severity and course of disease.

 

EPP is caused by decreased ferrochelatase activity resulting in significantly increased noncomplexed (free) protoporphyrin levels in erythrocytes, plasma, and feces.

 

XLDPP is caused by gain-of-function variants in the C-terminal end of ALAS2 gene and results in elevated erythrocyte levels of free and zinc-complexed protoporphyrin, and total protoporphyrin levels in plasma and feces.

 

Protoporphyrin fractionation is the main component of erythrocyte porphyrins. When total erythrocyte porphyrins are elevated, fractionation and quantitation of zinc-complexed and free protoporphyrin is necessary to differentiate the inherited porphyrias from other causes of elevated porphyrin levels. Other possible causes of elevated erythrocyte zinc-complexed protoporphyrin may include:

-Iron-deficiency anemia, the most common cause

-Chronic intoxication by heavy metals (primarily lead) or various organic chemicals

-Congenital erythropoietic porphyria (CEP), a rare autosomal recessive porphyria caused by deficient uroporphyrinogen III synthase

-Hepatoerythropoietic porphyria, a rare autosomal recessive porphyria caused by deficient uroporphyrinogen decarboxylase

 

Typically, the workup of patients with a suspected porphyria is most effective when following a stepwise approach. See Porphyria (Acute) Testing Algorithm and Porphyria (Cutaneous) Testing Algorithm in Special Instructions or call 800-533-1710 to discuss testing strategies.

 

There are 2 test options:

-PEE / Porphyrins Evaluation, Whole Blood

-PEWE / Porphyrins Evaluation, Washed Erythrocytes.

The whole blood option is easiest for clients but requires that the specimen arrive at Mayo Clinic Laboratories within 7 days of collection. When this cannot be ensured, washed frozen erythrocytes, which are stable for 14 days, should be submitted.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

PORPHYRINS, TOTAL, RBC

<80 mcg/dL

Interpretation Provides information to assist in interpretation of the test results

Abnormal results are reported with a detailed interpretation that may include an overview of the results and their significance, a correlation to available clinical information provided with the specimen, differential diagnosis, and recommendations for additional testing when indicated and available.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Alcohol suppresses enzyme activity potentially leading to false-positive results if it is ingested within 24 hours of specimen collection.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Tortorelli S, Kloke K, Raymond K: Chapter 15: Disorders of porphyrin metabolism. In Biochemical and Molecular Basis of Pediatric Disease. Fourth edition. Edited by DJ Dietzen, MJ Bennett, ECC Wong. AACC Press 2010, pp 307-324

2. Badminton MN, Whatley SD, Sardh E, Aarsand AK: Porphyrins and the porphyrias. In Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics. Sixth edition. Edited by N Rifai, AR Horvath, C Wittwer. Elsevier, Inc. 2018, pp 776-799

3. Anderson KE, Sassa S, Bishop DF, Desnick RJ: Disorders of Heme Biosynthesis: X-Linked Sideroblastic Anemia and the Porphyrias. In The Online Metabolic and Molecular Bases of Inherited Disease. Edited by D Valle, AL Beaudet, B Vogelstein, et al. New York, McGraw-Hill. Accessed August 2, 2019. Available at http://ommbid.mhmedical.com/content.aspx?bookid=971&Sectionid=62638866

4. Whatley SD, Ducamp S, Gouya B, et al: C-terminal deletions in the ALAS2 gene lead to gain of function and cause X-linked dominant protoporphyria without anemia or iron overload. Am J Hum Genet 2008 Sep;83(3):408-414

5. Balwani M, Naik H, Anderson KE, et al: Clinical, Biochemical, and Genetic Characterization of North American Patients with Erythropoietic Protoporphyria and X-linked Protoporphyria. JAMA Dermatol 2017 Aug 1;153(8):789-796

Special Instructions Library of PDFs including pertinent information and forms related to the test