Clinical, biochemical, and genetic study of 11 patients with erythropoietic protoporphyria including one with homozygous disease.

Abstract

OBJECTIVE:

To study the mutations in the ferrochelatase gene (FECH) and the phenotypic expression of erythropoietic protoporphyria (EPP) in a group of Spanish patients.

DESIGN:

Case series.

SETTING:

University-based hospital.

PATIENTS:

Eleven unrelated patients with EPP and 19 asymptomatic relatives from 10 families.

MAIN OUTCOMES MEASURES:

Measurement of protoporphyrin concentration in red blood cells and feces by fluorometry and chromatography. Analysis of the mutations of the FECH gene by single-strand conformation analysis. Expression of mutations in Escherichia coli.

RESULTS:

FECH gene mutations were found in all 11 patients. Ten were heterozygous and carried the IVS3-48C low-expression allele. Three novel mutations were found: IVS4 + 1delG, 347-351delC, and 130_147dupl 18. One patient did not present the IVS3-48C polymorphism and was found to harbor a novel A185T missense mutation in both alleles. The familial study confirmed a recessive mode of inheritance of the disease. The A185T mutation showed a residual activity 4% of normal when expressed in E coli. This patient presented cutaneous photosensitivity similar to the heterozygous cases, but a higher protoporphyrin accumulation in erythrocytes, microcytic anemia, and early signs of liver engagement. FECH mutations were found in 10 healthy relatives, none of whom carried the low-expression allele. The frequency of the IVS3-48C allele among 180 nonporphyric Spanish individuals was 5.2%.

CONCLUSIONS:

These findings confirm, among a group of Spanish patients, that most cases of EPP result from the coinheritance of IVS3-48C and a mutation in the FECH gene, and also document the existence of patients with mutations in homozygosity that may present a more severe form of the disease.

• Authors: Carmen Herrero, Jordi To-Figueras, Celia Badenas, Manuel Méndez, Patricia Serrano, Rafael Enríquez-Salamanca, Mario Lecha
• Journal: Archives of dermatology (Arch Dermatol) Vol. 143 Issue 9 Pg. 1125-9 (Sep 2007) ISSN: 0003-987X [Print] United States
• PMID: 17875872 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Protoporphyrins
• Ferrochelatase

Topics

• Adolescent
• Adult
• Child
• Child, Preschool
• Female
• Ferrochelatase (genetics)
• Homozygote
• Humans
• Male
• Mutation
• Phenotype
• Polymorphism, Single-Stranded Conformational
• Protoporphyria, Erythropoietic (diagnosis, genetics, metabolism)
• Protoporphyrins (metabolism)