Porphyrins Evaluation, Whole Blood
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 an enzyme deficiency in the heme biosynthetic pathway. Depending on which enzyme is deficient, various porphyrins and their precursors accumulate in plasma, erythrocytes, and tissues, and are excreted in the urine, feces, or both.
The porphyrias can be classified as either erythropoietic or hepatic. Both the erythropoietic porphyrias and the chronic hepatic porphyrias are associated with cutaneous photosensitivity, but not with the neurological symptoms that accompany the acute hepatic porphyrias. Diagnosis of the erythropoietic porphyrias (ie, erythropoietic protoporphyria: EPP and congenital erythropoietic porphyria: CEP) can be determined by analysis of porphyrins in the erythrocytes.
Erythrocyte (RBC) porphyrins consist almost entirely of protoporphyrin. Increased RBC protoporphyrin is characteristic of EPP, X-linked dominant protoporphyria (XLDPP), and of the intoxication porphyrias that may be caused by heavy metals, halogenated solvents, some pesticides, and medications. However, iron-deficiency anemia is the most common cause of increased RBC protoporphyrin. Therefore, when total RBC porphyrins are elevated, fractionation and quantitation of zinc-complexed and noncomplexed (free) protoporphyrin are necessary to differentiate the inherited porphyrias from other causes of elevated porphyrin levels.
Zinc-complexed protoporphyrin may be increased in RBCs in association with:
-Iron-deficiency anemia (the most common cause of elevated zinc protoporphyrin)
-Chronic intoxication by heavy metals (primarily lead) or various organic chemicals
-Hepatoerythropoietic porphyria, a rare form of porphyria caused by homozygous or compound heterozygous mutations in the uroporphyrinogen decarboxylase gene (UROD)
-XLDPP, a form of protoporphyria caused by a gain-of-function mutation in the C-terminal end of ALAS2 gene
Free protoporphyrin is increased in RBCs in association with EPP, an erythropoietic porphyria that is inherited in an autosomal dominant fashion. EPP is considered to be the third most common form of porphyria. It is caused by diminished ferrochelatase activity, which results in increased free protoporphyrin levels in RBCs, plasma, and feces. Onset of symptoms typically occurs in childhood with cutaneous photosensitivity in sun-exposed areas of the skin, generally becoming worse 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. Similar clinical phenotype and elevation of total protoporphyrin (40% of which is zinc-complexed) is seen in patients affected by XLDPP, which results from increased activity of 5-aminolevulinate synthase (ALAS2).
CEP is an erythropoietic porphyria that is inherited in an autosomal recessive fashion. CEP is caused by uroporphyrinogen III (co-)synthase (UROS) deficiency, which results in the accumulation and excretion of uroporphyrin I and coproporphyrin I in urine and feces. Circulating RBCs contain measurable amounts of uroporphyrin and coproporphyrin. RBC zinc protoporphyrin may also be elevated due to increased erythropoiesis. Symptoms typically present in early infancy with red-brown staining of diapers, severe cutaneous photosensitivity with fluid-filled bullae and vesicles. Other common symptoms may include thickening of the skin, hypo- and hyperpigmentation, hypertrichosis, cutaneous scarring, and deformities of the fingers, eyelids, lips, nose, and ears.
Diagnosis of erythropoietic protoporphyria and congenital erythropoietic porphyria
Evaluation of chronic intoxication from exposure to a variety of agents including heavy metals and chemicals
Differentiating iron-deficiency anemia from other causes of elevated porphyrin levels
An elevation of total RBC porphyrins can be an expression of a primary or secondary defect in the biosynthesis of heme. However, the specific type of porphyria cannot be determined by total porphyrin analysis alone.
Total RBC porphyrin values >80 mcg/dL suggest the existence of an intoxication problem or a metabolic problem that involves accelerated erythropoiesis. If the total RBC porphyrin concentration is elevated, additional testing (fractionation assays) is required to identify and quantify the specific affected porphyrin. Increased total RBC porphyrin concentrations may be due to:
-Free protoporphyrin, the predominant form that is elevated in patients with erythropoietic protoporphyria
-Zinc protoporphyrin, elevated in patients with heavy metal intoxication or iron deficiency anemia
A written interpretation is included with all reports. When abnormal results are detected, a detailed interpretation is given, including:
-An overview of the results and their significance
-Elements of a differential diagnosis
-Recommendations for additional biochemical testing
A normal RBC porphyrin evaluation does not rule out other forms of porphyria including porphyria cutanea tarda (PCT), acute intermittent porphyria (AIP), hereditary coproporphyria (HCP), and variegate porphyria (VP).
See The Heme Biosynthetic Pathway in Special Instructions.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Abstinence from alcohol for at least 24 hours prior to specimen collection is essential as ethanol induces some enzyme activity and suppresses other enzymes along the heme biosynthetic pathway.
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 48 hours of draw. When this cannot be ensured, washed RBCs should be submitted.
It is essential to proceed expeditiously with obtaining, processing, and dispatching the specimen, paying special heed to maintaining low temperatures (see Specimen Required). Failure to adhere to these directions may result in analyte degradation, yielding false-negative values.
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 packed cells
<20 mcg/dL packed cells
<60 mcg/dL packed cells
Clinical References Provides recommendations for further in-depth reading of a clinical nature
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. Ellefson RD: Porphyrinogens, porphyrins and the porphyrias. Mayo Clin Proc 1982;57:454-458
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