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). CONTENT: 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. SUMMARY: 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.
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). CONTENT: 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. SUMMARY: 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.
Authors: Sharon D Whatley; Sarah Ducamp; Laurent Gouya; Bernard Grandchamp; Carole Beaumont; Michael N Badminton; George H Elder; S Alexander Holme; Alexander V Anstey; Michelle Parker; Anne V Corrigall; Peter N Meissner; Richard J Hift; Joanne T Marsden; Yun Ma; Giorgina Mieli-Vergani; Jean-Charles Deybach; Hervé Puy Journal: Am J Hum Genet Date: 2008-09-04 Impact factor: 11.025
Authors: Janneke G Langendonk; Manisha Balwani; Karl E Anderson; Herbert L Bonkovsky; Alexander V Anstey; D Montgomery Bissell; Joseph Bloomer; Chris Edwards; Norbert J Neumann; Charles Parker; John D Phillips; Henry W Lim; Iltefat Hamzavi; Jean-Charles Deybach; Raili Kauppinen; Lesley E Rhodes; Jorge Frank; Gillian M Murphy; Francois P J Karstens; Eric J G Sijbrands; Felix W M de Rooij; Mark Lebwohl; Hetanshi Naik; Colin R Goding; J H Paul Wilson; Robert J Desnick Journal: N Engl J Med Date: 2015-07-02 Impact factor: 91.245
Authors: Manisha Balwani; Dana Doheny; David F Bishop; Irina Nazarenko; Makiko Yasuda; Harry A Dailey; Karl E Anderson; D Montgomery Bissell; Joseph Bloomer; Herbert L Bonkovsky; John D Phillips; Lawrence Liu; Robert J Desnick Journal: Mol Med Date: 2013-04-30 Impact factor: 6.354
Authors: Manisha Balwani; Hetanshi Naik; Karl E Anderson; D Montgomery Bissell; Joseph Bloomer; Herbert L Bonkovsky; John D Phillips; Jessica R Overbey; Bruce Wang; Ashwani K Singal; Lawrence U Liu; Robert J Desnick Journal: JAMA Dermatol Date: 2017-08-01 Impact factor: 10.282