Elder G H
Department of Medical Biochemistry, University of Wales College of Medicine, Heath Park, Cardiff, UK.
Photodermatol Photoimmunol Photomed. 1998 Apr;14(2):66-9. doi: 10.1111/j.1600-0781.1998.tb00014.x.
Each porphyria results from decreased activity of one of the enzymes of haem biosynthesis. The molecular basis of enzyme deficiencies in acute intermittent porphyria (AIP), variegate porphyria (VP) and congenital erythropoietic porphyria (CEP) is outlined. All three conditions show extensive allelic heterogeneity. In the autosomal dominant disorders, AIP and VP, no genotype/phenotype correlations have been demonstrated, and the explanation for their low clinical penetrance remains uncertain. In AIP and VP, mutational analysis is superior to biochemical methods for screening families for latent porphyria. In the autosomal recessive condition, CEP, there is some genotype/phenotype correlation--one common mutation (C73R) being associated with severe disease in homozygotes. Porphyria cutanea tarda (PCT) is not a simple monogenic disorder. Patients appear to have an inherited susceptibility to inactivation of hepatic uroporphyrinogen decarboxylase (UROD) as part of a response to hepatocyte injury by alcohol, HCV and other agents. Inherited factors that, in combination, may predispose to PCT include mutations in the UROD gene, present in about 20% of patients, and the C282Y mutation in the haemochromatosis (HFE) gene.
每种卟啉病都是由于血红素生物合成过程中一种酶的活性降低所致。本文概述了急性间歇性卟啉病（AIP）、混合型卟啉病（VP）和先天性红细胞生成性卟啉病（CEP）中酶缺乏的分子基础。这三种疾病均表现出广泛的等位基因异质性。在常染色体显性疾病AIP和VP中，尚未证实基因型与表型之间存在相关性，其临床低外显率的原因仍不确定。在AIP和VP中，突变分析在筛查潜在卟啉病家族方面优于生化方法。在常染色体隐性疾病CEP中，存在一些基因型与表型的相关性——一种常见突变（C73R）与纯合子中的严重疾病相关。迟发性皮肤卟啉病（PCT）并非简单的单基因疾病。患者似乎具有遗传性易感性，易导致肝脏尿卟啉原脱羧酶（UROD）失活，这是对酒精、丙型肝炎病毒和其他因素引起的肝细胞损伤的一种反应。可能共同导致PCT的遗传因素包括UROD基因突变（约20%的患者存在该突变）以及血色素沉着症（HFE）基因中的C282Y突变。
