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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 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 exacerbate symptoms, significantly impacting the severity and course of disease.
EPP is caused by diminished ferrochelatase activity resulting in significantly increased free protoporphyrin levels in RBCs, plasma, and/or feces.
X-linked dominant protoporphyria is caused by mutations in the C-terminal end of ALAS2 gene and results in elevated RBC levels of free and zinc-complexed protoporphyrin.
RBC porphyrins consist almost entirely of protoporphyrin. When total RBC porphyrins are elevated, fractionation and quantitation of zinc-complexed and free protoporphyrin are necessary to differentiate the inherited porphyrias from other causes of elevated porphyrin levels. Potential explanations for elevated RBC zinc-complexed protoporphyrin may include:
-Iron deficiency anemia, the most common cause of increased total RBC protoporphyrin
-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 (HEP), 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 contact Mayo Medical Laboratories to discuss testing strategies.
Establishing a differential diagnosis of erythropoietic protoporphyria, X-linked dominant protoporphyria, iron-deficiency anemia, and chronic lead intoxication
Abnormal results are reported with a detailed interpretation which 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.
The preferred test for lead toxicity in children is blood lead (see PBBD / Lead with Demographics, Blood).
Patients must abstain from alcohol for at least 24 hours. Alcohol suppresses enzyme activity potentially leading to false-positive results.
There are 2 test options: PEE / Porphyrins Evaluation, Whole Blood and PEWE / Porphyrins Evaluation, Washed Erythrocytes. The whole blood option is easiest for clients but requires that the specimen arrive at Mayo Medical Laboratories within 7 days of draw. When this cannot be ensured, washed frozen RBCs should be submitted.
PORPHYRINS, TOTAL, RBC
<80 mcg/dL packed cells
<20 mcg/dL packed cells
<60 mcg/dL packed cells
1. Nuttall KL, Klee GG: Analytes of hemoglobin metabolism-porphyrins, iron and bilirubin. In Tietz Fundamentals of Clinical Chemistry. Fifth edition. Edited by CA Burtis, ER Ashwood. Philadelphia, WB Saunders Company, 2001, pp 584-607
2. 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
3. Anderson KE, Sassa S, Bishop DF, Desnick RJ: Disorders of heme biosynthesis: X-linked sideroblastic anemia and the porphyrias. In The Metabolic Basis of Inherited Disease. Eighth edition. Edited by CR Scriver, AL Beaudet, WS Sly, et al. New York, McGraw-Hill Medical Published Division, 2001, pp 2991-3062
4. Sassa S: Modern diagnosis and management of the porphyrias. Br J Haematol 2006;135:281-292
5. 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