Autosomal recessive erythropoietic protoporphyria in the United Kingdom: prevalence and relationship to liver disease

• Published in: Journal of medical genetics Vol. 41; no. 8; p. e105
• Main Authors: Whatley, S D, Mason, N G, Khan, M, Zamiri, M, Badminton, M N, Missaoui, W N, Dailey, T A, Dailey, H A, Douglas, W S, Wainwright, N J, Elder, G H
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group Ltd 01-08-2004; BMJ Publishing Group LTD; BMJ Group
• Subjects: Adolescent; Adult; Aged; alanine aminotransferase; Alleles; ALT; aspartate transaminase; AST; autosomal recessive; Biosynthesis; Child; Child, Preschool; Confidence intervals; Deoxyribonucleic acid; DNA; EPP; erythropoietic protoporphyria; FECH; Female; ferrochelatase; Ferrochelatase - genetics; ferrochelatase mutations; gamma glutamyl transpeptidase; Genes, Recessive - genetics; Genotype & phenotype; GGT; Hematology; Humans; Infant; Liver cirrhosis; liver disease; Liver diseases; Liver Diseases - epidemiology; Liver Diseases - genetics; Male; Middle Aged; Mutation; Online Mutation Report; Patients; Prevalence; Protoporphyria, Erythropoietic - enzymology; Protoporphyria, Erythropoietic - epidemiology; Protoporphyria, Erythropoietic - genetics; single nucleotide polymorphism; SNP; United Kingdom; United Kingdom > UK; France
• ISSN: 0022-2593; 1468-6244; 1468-6244
• DOI: 10.1136/jmg.2003.016121

6- 10 Most individuals who are heterozygous for these mutations are asymptomatic, despite having half-normal FECH activities. 11 For protoporphyrin to accumulate sufficiently to cause photosensitivity, reduction of FECH activity to below a critical threshold of about 35% of normal is required. 11- 14 In most patients, this additional reduction results from inheritance of a low expression FECH allele trans to a severe mutation. 10, 15- 18 The low expression allele is the C variant of a single nucleotide polymorphism (SNP; IVS3-48C/T) in intron 3 of the FECH gene. 18 Because the IVS3-48C allele is common in the general population, being present in about 11% of the white inhabitants of France, 18 inheritance trans to a severe FECH mutation occurs within EPP families at a frequency that is high enough to produce a pattern of inheritance of overt EPP resembling an autosomal dominant disease with incomplete penetrance. [...]autosomal recessive EPP appears to be clinically indistinguishable from EPP in which an FECH mutation on one allele is trans to a low expression IVS3-48C allele but may carry a much higher risk of severe liver disease.