Clinical, biochemical, and genetic study of 11 patients with erythropoietic protoporphyria including one with homozygous disease.
OBJECTIVE
To study the mutations in the ferrochelatase gene (FECH) and the phenotypic expression of erythropoietic protoporphyria (EPP) in a group of Spanish patients.


METHODS
Case series.


METHODS
University-based hospital.


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


METHODS
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.
Herrero
Carmen
C
Department of Dermatology, Hospital Clinic of Barcelona, University of Barcelona, IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), Barcelona, Spain.
To-Figueras
Jordi
J
Badenas
Celia
C
Méndez
Manuel
M
Serrano
Patricia
P
Enríquez-Salamanca
Rafael
R
Lecha
Mario
M
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D005294:Ferrochelatase / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008297:Male; D009154:Mutation; D010641:Phenotype; D018807:Polymorphism, Single-Stranded Conformational; D046351:Protoporphyria, Erythropoietic / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D011524:Protoporphyrins / Q000378:metabolism
D011524:Protoporphyrins; D005294:Ferrochelatase