Clinical, Biochemical, and Genetic Study of 11 Patients With Erythropoietic Protoporphyria Including One With Homozygous Disease

Abstract

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: IVS4ϩ 1delG, 347-351delC, and 130_147dupl 18. One

Novel Null-Allele Mutations and Genotype-Phenotype Correlation in Argentinean Patients with Erythropoietic Protoporphyria

“…These findings are in agreement with the conclusion that the inheritance of a lowexpressed allele together with the mutation in the FECH gene are necessary for the clinical expression of this porphyria (4,13,14,16,(25)(26)(27).…”

Molecular epidemiology of erythropoietic protoporphyria in the U.K.

“…Our data show that, as in other countries, 6,9,[15][16][17][18][19][20] several different FECH mutations are found in EPP in the U.K. However, allelic heterogeneity is less than for the autosomal dominant acute porphyrias, 21 largely due to the presence of a single large extended family with the mutation c.314 + 2T>G. Similarly high frequencies of a single mutation among apparently unrelated families have been reported for EPP in Northern Ireland, 22 in South Africans of European descent 9 and in Switzerland.…”

Seasonal Palmar Keratoderma in Erythropoietic Protoporphyria Indicates Autosomal Recessive Inheritance

“…Developmental delay has been reported in the recessive or ''homozygous'' forms of the dominant acute porphyrias, usually in association with other neurological and skeletal abnormalities (Elder, 1997), which were not seen in our patients. Also, 5 of the 12 (42%) reported patients with autosomal recessive EPP, in which keratoderma was apparently not present, had liver disease (Sarkany et al, 1994a;Whatley et al, 2004;Gouya et al, 2006;Herrero et al, 2007). In contrast, none of our nine patients had liver dysfunction.…”

“…However, it seems unlikely that keratoderma has been overlooked in all previously reported patients with recessive EPP. Where clinical descriptions have been provided (Lamoril et al, 1991;Sarkany et al, 1994a;Herrero et al, 2007), it has not been noted and three of the patients with recessive disease that we have identified (this report; Whatley et al, 2004) did not have keratoderma.…”