Lajic S, Bui T H, Holst M, Ritzén M, Wedell A
Institutionen f r kvinnors och barns hälsa, Karolinska sjukhuset, Stockholm.
Lakartidningen. 1997 Dec 10;94(50):4781-6.
Congenital adrenal hyperplasia (CAH) is the common name of a constellation of diseases that impair cortisol synthesis in the adrenal cortex. As defects in each of three steroidogenic enzymes, 21-hydroxylase, 11 beta-hydroxylase, and 3 beta-hydroxysteroid dehydrogenase, promote overproduction of adrenal androgens, affected female fetuses may be virilised. The major cause of CAH is 21-hydroxylase deficiency, the incidence of which is 1:10,000 live births in the Swedish population. Of the 10-15 children born in Sweden each year with 21-hydroxylase deficiency, 3-5 will be virilised girls who must undergo traumatic surgery of the external genitalia. This can be prevented by administration of dexamethasone to the gravida during pregnancy. Prenatal treatment was introduced in Sweden in 1985, prenatal diagnosis being based in most cases on direct mutational analysis using allele-specific PCR on DNA from chorionic villus samples. In our experience, genotype corresponds well to phenotype, and we recommend that all children with 21-hydroxylase deficiency be genotyped in order to prepare the family for rapid and reliable prenatal diagnosis and possible treatment when the next child is awaited. Since 1985, 35 women have received prenatal treatment in Sweden, six of the 35 fetuses being found to be affected females and treated until term. As compared with their older sisters, all of these six girls were characterised by no signs, or only minor signs, of virilisation, and only one required surgery because of labial fusion and recurrent urinary tract infections. As a group, the 35 infants were characterised by normal birth weight and length, and normal growth during the first year of life. Passage of developmental milestones was normal though several adverse events, both in treated mothers and infants, have been reported. Approximately one fourth of the women treated throughout pregnancy reported some side-effect (e.g., excessive weight gain, severe cutaneous striae, mood fluctuations and irritability, acne and hirsutism, or oedema). One unaffected boy, treated for seven weeks, was born with severe hydrocephalus and agenesis of the corpus callosum; two affected sisters and one unaffected girl were characterised by failure to thrive during the first year of life, but later recovered (one of the affected sisters was later diagnosed as suffering from mitochondrial disease). Although in our experience prenatal treatment with dexamethasone is effective in preventing virilisation of girls with 21-hydroxylase deficiency, some adverse events have been noted in treated infants. As it remains unknown whether these events were attributable to the treatment, it must still be regarded as experimental, and its use should be centralised and meticulously monitored until more experience has been gained.
先天性肾上腺皮质增生症（CAH）是一组损害肾上腺皮质中皮质醇合成的疾病的统称。由于三种类固醇生成酶（21-羟化酶、11β-羟化酶和3β-羟类固醇脱氢酶）中的每一种存在缺陷，都会促进肾上腺雄激素的过量产生，受影响的女胎可能会出现男性化。CAH的主要原因是21-羟化酶缺乏，在瑞典人群中其发病率为1:10000活产。在瑞典每年出生的10 - 15名患有21-羟化酶缺乏症的儿童中，3 - 5名将是男性化的女孩，她们必须接受外阴的创伤性手术。这可以通过在孕期给孕妇使用地塞米松来预防。瑞典于1985年引入了产前治疗，大多数情况下产前诊断基于对绒毛膜绒毛样本DNA进行等位基因特异性PCR的直接突变分析。根据我们的经验，基因型与表型对应良好，我们建议对所有21-羟化酶缺乏症患儿进行基因分型，以便为家庭做好准备，在期待下一个孩子时能够进行快速可靠的产前诊断并可能进行治疗。自1985年以来，瑞典有35名女性接受了产前治疗，35名胎儿中有6名被发现是受影响的女性，并一直治疗至足月。与她们的姐姐相比，这6名女孩均无男性化迹象或仅有轻微迹象，只有一名因阴唇融合和反复尿路感染而需要手术。作为一个群体，这35名婴儿的特点是出生体重和身长正常，在生命的第一年生长正常。发育里程碑的进展正常，不过已有报道称治疗的母亲和婴儿都出现了一些不良事件。在整个孕期接受治疗的女性中，约四分之一报告有一些副作用（如体重过度增加、严重的皮肤条纹、情绪波动和易怒、痤疮和多毛症或水肿）。一名接受了7周治疗的未受影响男孩出生时患有严重脑积水和胼胝体发育不全；两名受影响的姐妹和一名未受影响的女孩在生命的第一年生长发育不良，但后来恢复了（其中一名受影响的姐妹后来被诊断患有线粒体疾病）。尽管根据我们的经验，地塞米松产前治疗可有效预防21-羟化酶缺乏症女孩的男性化，但在接受治疗的婴儿中已注意到一些不良事件。由于尚不清楚这些事件是否归因于治疗，它仍必须被视为实验性的，在获得更多经验之前，其使用应集中进行并受到严格监测。
