Backgro(1575und: Congenital erythropoietic porphyria (CEP) is a rare autosomal recessive disease caused by the deficient activity of the heme biosynthetic enzyme, uroporphyrinogen III synthase (URO-synthase), and the ...Backgro(1575und: Congenital erythropoietic porphyria (CEP) is a rare autosomal recessive disease caused by the deficient activity of the heme biosynthetic enzyme, uroporphyrinogen III synthase (URO-synthase), and the accumulation of the non physiologic and phototoxic porphyrin I isomers. Clinical manifestations range from severe mutilation to mild erosions and blisters on sun-exposed areas. Evaluation of the URO-synthase mutation and residual enzyme activity has been correlated with the phenotypic expression of the disease. Observations: We describe 16- and 4-year-old brothers with CEP with a mild phenotype due to a novel genotype,one allele having a promoter mutation (- 76G→ A) and the other having an exonic missense mutation (G225S). The father and a 4-year-old fraternal twin brother were carriers of the - 76G→ A mutation, whereas the mother and a 16-year-old brother were carriers of the G225S mutation. Previous in vitro expression studies demonstrated that the G225S mutation severely decreased URO-synthase activity to 1.2% of normal, whereas the promoter mutation decreased the activity to approximately 50% of wild type, accounting for the mild clinical phenotype. Conclusion: The mild disease phenotype in these patients is a further example of the clinical heterogeneity seen in CEP and is additional proof that in vitro enzyme expression studies provide dependable genotype-phenotype correlations.展开更多
文摘Backgro(1575und: Congenital erythropoietic porphyria (CEP) is a rare autosomal recessive disease caused by the deficient activity of the heme biosynthetic enzyme, uroporphyrinogen III synthase (URO-synthase), and the accumulation of the non physiologic and phototoxic porphyrin I isomers. Clinical manifestations range from severe mutilation to mild erosions and blisters on sun-exposed areas. Evaluation of the URO-synthase mutation and residual enzyme activity has been correlated with the phenotypic expression of the disease. Observations: We describe 16- and 4-year-old brothers with CEP with a mild phenotype due to a novel genotype,one allele having a promoter mutation (- 76G→ A) and the other having an exonic missense mutation (G225S). The father and a 4-year-old fraternal twin brother were carriers of the - 76G→ A mutation, whereas the mother and a 16-year-old brother were carriers of the G225S mutation. Previous in vitro expression studies demonstrated that the G225S mutation severely decreased URO-synthase activity to 1.2% of normal, whereas the promoter mutation decreased the activity to approximately 50% of wild type, accounting for the mild clinical phenotype. Conclusion: The mild disease phenotype in these patients is a further example of the clinical heterogeneity seen in CEP and is additional proof that in vitro enzyme expression studies provide dependable genotype-phenotype correlations.
