Hughes I A
Department of Paediatrics, University of Cambridge, Addenbrooke's Hospital, Box 116, Hills Road, Cambridge CB2 2QQ, UK.
Semin Reprod Med. 2002 Aug;20(3):229-42. doi: 10.1055/s-2002-35387.
Congenital adrenal hyperplasia is a family of monogenic autosomal recessive disorders of steroidogenesis with protean clinical manifestations. The commonest form, 21-hydroxylase deficiency, is the most frequent cause of ambiguous genitalia in the newborn. The molecular features associated with abnormalities in the CYP21 gene are well characterized in relation to phenotypic manifestations. The concordance between genotype and phenotype is sufficiently robust as to be relevant and useful in planning treatment strategies. Thus, the dose of glucocorticoid replacement in the early years of life can be tailored according to the predicted degree of 21-hydroxylase enzyme deficiency in the anticipation that this may avoid hitherto excessive steroid replacement during the critical early years of growth and development. The means to prevent genital virilization in affected females is clearly demonstrated by the success of early dexamethasone administration to pregnant mothers at risk. Short-term outcome studies of children exposed to dexamethasone in utero indicate no significant adverse effects. Nevertheless, it is recommended that prenatal treatment programs to prevent a major congenital malformation of the urogenital system be conducted only as part of agreed national multicenter studies, which include a commitment to long-term outcome analyses.
先天性肾上腺皮质增生症是一类具有多样临床表现的单基因常染色体隐性类固醇生成障碍疾病。最常见的类型，即21-羟化酶缺乏症，是新生儿生殖器模糊的最常见原因。与CYP21基因异常相关的分子特征已根据表型表现得到充分表征。基因型与表型之间的一致性足够强，在制定治疗策略时具有相关性和实用性。因此，生命早期的糖皮质激素替代剂量可以根据预测的21-羟化酶缺乏程度进行调整，以期在生长发育的关键早期避免迄今过度的类固醇替代。对有风险的孕妇早期给予地塞米松成功地证明了预防受影响女性生殖器男性化的方法。对子宫内接触地塞米松的儿童进行的短期结局研究表明没有明显的不良影响。然而，建议仅作为商定的国家多中心研究的一部分开展预防泌尿生殖系统重大先天性畸形的产前治疗项目，其中包括对长期结局分析的承诺。
