Pitfalls in Erythrocyte Protoporphyrin Measurement for Diagnosis and Monitoring of Protoporphyrias.
BACKGROUND
Laboratory diagnosis of erythropoietic protoporphyria (EPP) requires a marked increase in total erythrocyte protoporphyrin (300-5000 μg/dL erythrocytes, reference interval <80 μg/dL) and a predominance (85%-100%) of metal-free protoporphyrin [normal, mostly zinc protoporphyrin (reference intervals for the zinc protoporphyrin proportion have not been established)]; plasma porphyrins are not always increased. X-linked protoporphyria (XLP) causes a similar increase in total erythrocyte protoporphyrin with a lower fraction of metal-free protoporphyrin (50%-85% of the total).


BACKGROUND
In studying more than 180 patients with EPP and XLP, the Porphyrias Consortium found that erythrocyte protoporphyrin concentrations for some patients were much higher (4.3- to 46.7-fold) than indicated by previous reports provided by these patients. The discrepant earlier reports, which sometimes caused the diagnosis to be missed initially, were from laboratories that measure protoporphyrin only by hematofluorometry, which is intended primarily to screen for lead poisoning. However, the instrument can calculate results on the basis of assumed hematocrits and reports results as "free" and "zinc" protoporphyrin (with different reference intervals), implying separate measurements of metal-free and zinc protoporphyrin. Such misleading reports impair diagnosis and monitoring of patients with protoporphyria.


CONCLUSIONS
We suggest that laboratories should prioritize testing for EPP and XLP, because accurate measurement of erythrocyte total and metal-free protoporphyrin is essential for diagnosis and monitoring of these conditions, but less important for other disorders. Terms and abbreviations used in reporting erythrocyte protoporphyrin results should be accurately defined.
University of Texas Medical Branch, Galveston, TX;
Eric W
EW
Gou
Icahn School of Medicine at Mt. Sinai, New York, NY;
Manisha
M
Balwani
University of California at San Francisco, San Francisco, CA;
D Montgomery
DM
Bissell
University of Alabama at Birmingham, Birmingham, AL;
Joseph R
JR
Bloomer
Wake Forest University, Winston-Salem, NC;
Herbert L
HL
Bonkovsky
Icahn School of Medicine at Mt. Sinai, New York, NY;
Robert J
RJ
Desnick
Icahn School of Medicine at Mt. Sinai, New York, NY;
Hetanshi
H
Naik
University of Utah, Salt Lake City, UT;
John D
JD
Phillips
University of Alabama at Birmingham, Birmingham, AL;
Ashwani K
AK
Singal
University of California at San Francisco, San Francisco, CA;
Bruce
B
Wang
University of Washington, Seattle, WA.
Sioban
S
Keel
University of Texas Medical Branch, Galveston, TX; kanderso@utmb.edu.
Karl E
KE
Anderson
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003937:Diagnosis, Differential; D004912:Erythrocytes / Q000737:chemistry*; D005260:Female; D005470:Fluorometry / Q000379:methods; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007855:Lead Poisoning / Q000097:blood / Q000175:diagnosis*; D008297:Male; D011164:Porphyrias / Q000097:blood / Q000175:diagnosis*; D046351:Protoporphyria, Erythropoietic / Q000097:blood / Q000175:diagnosis*; D011524:Protoporphyrins / Q000097:blood*; D011933:Reagent Kits, Diagnostic / Q000592:standards; D012016:Reference Values
D011524:Protoporphyrins; D011933:Reagent Kits, Diagnostic; C017803:zinc protoporphyrin; C028025:protoporphyrin IX