Protoporphyrins, Fractionation, Whole Blood
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Erythrocyte (RBC) porphyrins consist almost entirely of protoporphyrin. Increased RBC protoporphyrin is characteristic of erythropoietic protoporphyria (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 can be increased in erythrocytes in association with:
-Iron deficiency anemia (the most common cause of elevated zinc protoporphyrin)
-Chronic intoxication by heavy metals (ie, 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).
The following algorithms are available in Special Instructions:
-Porphyria (Acute) Testing Algorithm
-Porphyria (Cutaneous) Testing Algorithm
Establishing a biochemical diagnosis of erythropoietic protoporphyria
Differential diagnosis of chronic intoxication from exposure to a variety of causes including heavy metals and chemicals
Differential diagnosis in some cases of iron-deficiency anemia
Values of zinc-complexed protoporphyrin >60 mcg/dL suggest iron deficiency anemia or may indicate chronic intoxication by heavy metals or organic chemicals.
A predominance of noncomplexed (free) protoporphyrin indicates a diagnosis of erythropoietic protoporphyria.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Abstinence from alcohol is essential for at least 24 hours as alcohol suppresses enzyme activity, potentially leading to false-negative results.
There are 2 test options: whole blood (PPFE / Protoporphyrins, Fractionation, Whole Blood) and washed RBCs (PPFWE / Protoporphyrins, Fractionation, Washed Erythrocytes). The whole blood option is easiest for clients but requires that the specimen arrive at Mayo Medical Laboratories within 72 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, precisely following the procedures specified in Specimen Required, paying special heed to maintaining low temperatures.
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.
<20 mcg/dL packed cells
<60 mcg/dL packed cells
See The Heme Biosynthetic Pathway in Special Instructions.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Ellefson RD: Porphyrinogens, porphyrins, and the porphyrias. Mayo Clin Proc 1982;57:454-458
2. 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 Book Company, 2001, pp 584-607
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 Publishing Division, 2001, pp 2991-3062
4. Whatley SD, Ducamp S, Gouya L, et al: C-terminal 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