Journal of Inherited Metabolic Disease

, Volume 31, Supplement 2, pp 363–367

Biochemical and molecular diagnosis of erythropoietic protoporphyria in an Ashkenazi Jewish family

  • X. Schneider-Yin
  • R. Mamet
  • E. I. Minder
  • N. Schoenfeld
Short Report

DOI: 10.1007/s10545-008-0924-8

Cite this article as:
Schneider-Yin, X., Mamet, R., Minder, E.I. et al. J Inherit Metab Dis (2008) 31(Suppl 2): 363. doi:10.1007/s10545-008-0924-8

Summary

Erythropoietic protoporphyria (EPP) is a rare hereditary disorder due to a partial deficiency of ferrochelatase (FECH). The genotype of EPP patients features a mutation on one allele of the FECH gene and a common hypomorphic FECH IVS3–48c on the other allele (M/c). The resulting enzyme activity in patients is ∼35% of that in normal individuals. Ferrochelatase deficiency results in the accumulation of protoporphyrin in the skin, which is responsible for the clinical symptom of cutaneous photosensitivity in patients. In this study, we report the identification of a novel FECH mutation delT23 in an 11-member EPP family of Jewish origin. Two EPP siblings shared an identical genotype of delT23/IVS3–48c (M/c). They were both photosensitive and showed highly increased erythrocyte protoporphyrin. The genotype of the patients’ mother, who did not present with any EPP clinical symptoms, was delT23/IVS3–48t (M/t). The patients’ father, an offspring of consanguineous parents, was homozygous IVS3–48 c/c. He exhibited a mild photosensitivity, and an increase of 4-fold in erythrocyte protoporphyrin. His FECH mRNA amount was 71% of that of genotype t/t. It is the first reported case of an individual with c/c genotype who exhibits both biochemical and clinical indications of EPP. These results suggest that IVS3–48c is a functional variant of ferrochelatase. The clinical symptoms and biochemical abnormalities in the patients’ father could be the result of an interaction between genetic and environmental factors. In addition, the frequency of IVS3–48c in the Ashkenazi Jewish population was estimated at 8%, which is similar to that in the European populations.

Abbreviations

EPP

erythropoietic protoporphyria

FECH

ferrochelatase

PCR

polymerase chain reaction

RBC

red blood cells

SNP

single nucleotide polymorphism

Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • X. Schneider-Yin
    • 1
  • R. Mamet
    • 2
  • E. I. Minder
    • 1
  • N. Schoenfeld
    • 2
    • 3
  1. 1.Zentrallabor, Stadtspital TriemliZürichSwitzerland
  2. 2.National Laboratory for the Biochemical Diagnoses of Porphyrias, Rabin Medical CenterBeilinson HospitalPetah-TikvaIsrael
  3. 3.Department of Human Molecular Genetics and Biochemistry, The Sackler Faculty of MedicineTel Aviv UniversityTel AvivIsrael