Molecular mechanisms of dominant expression in porphyria |
| |
Authors: | Email author" target="_blank">M?N?BadmintonEmail author G?H?Elder |
| |
Institution: | (1) Cardiff Porphyria Service, Department of Medical Biochemistry and Immunology, School of Medicine, Cardiff University, UK;(2) Cardiff Porphyria Service, Department of Medical Biochemistry and Immunology, School of Medicine, Cardiff University, Cardiff, CF14 4XN, UK |
| |
Abstract: | Summary Summary:#Partial deficiency of enzymes in the haem synthetic pathway gives rise to a group of seven inherited metabolic disorders,
the porphyrias. Each deficiency is associated with a characteristic increase in haem precursors that correlates with the symptoms
associated with individual porphyrias and allows accurate diagnosis. Two types of clinical presentation occur separately or
in combination; acute life-threatening neurovisceral attacks and/or cutaneous symptoms. Five of the porphyrias are low-penetrance
autosomal dominant conditions in which clinical expression results from additional factors that act by increasing demand for
haem or by causing an additional decrease in enzyme activity or by a combination of these effects. These include both genetic
and environmental factors. In familial porphyria cutanea tarda (PCTF), environmental factors that include alcohol, exogenous
oestrogens and hepatotropic viruses result in inhibition of hepatic enzyme activity via a mechanism that involves excess iron
accumulation. In erythropoietic protoporphyria (EPP), co-inheritance of a functional polymorphism in trans to a null ferrochelatase allele accounts for most clinically overt cases. In the autosomal dominant acute hepatic porphyrias
(acute intermittent porphyria, variegate porphyria, hereditary coproporphyria), acute neurovisceral attacks occur in a minority
of those who inherit one of these disorders. Although various exogenous (e.g. drugs, alcohol) and endogenous factors (e.g.
hormones) have been identified as provoking acute attacks, these do not provide a full explanation for the low penetrance
of these disorders. It seems probable that genetic background influences susceptibility to acute attacks, but the genes that
are involved have not yet been identified. |
| |
Keywords: | |
本文献已被 PubMed SpringerLink 等数据库收录! |
|