Pasqualini Titania, Alonso Guillermo, Tomasini Rosangela, Galich Ana Maria, Buzzalino Noemi, Fernandez Cecilia, Minutolo Carolina, Alba Liliana, Dain Liliana
Seccion de Endocrinología, Crecimiento y Desarrollo, Departamento de Pediatría, Hospital Italiano, Bueno Aires, Argentina.
Medicina (B Aires). 2007;67(3):253-61.
Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is a disorder which can adopt three clinical expressions: two classical forms -salt-wasting (SW), with residual enzymatic activity (EA) < or = 1% and simple virilizing (SV), with EA 1-2%- and a mild late onset or nonclassical (NC) form, with EA 10-60%. Our objective is to describe clinical characteristics, growth, and bone mass in a group of patients affected by 21-hydroxylase deficiency. Besides, molecular genetics studies were performed in patients, and also when available in their parents and siblings. Nine patients with neonatal diagnosis and 8 with pre or postpubertal diagnosis were studied. Analyses of 10-point mutations in the CYP21A2 gene were performed. We found that all the patients with the classical expression, except one with a de novo mutation R356W in one allele, were fully genotyped with predictive < 2% EA mutations. Signs of hyperandrogenism were present in 5/6 NC patients; one was diagnosed by searching for mutations in asymptomatic siblings. All the NC patients were compound heterozygotes carrying V281L mutation in one allele and a predictive low EA in the other, except for one not yet determined. In patients with neonatal diagnosis, mean height was low at one year of age, though it showed a significant increase before the onset of puberty. We conclude that neonatal diagnosis of classical CAH allows an adequate follow up enhancing growth. Molecular analyses of all members of an affected family may disclose asymptomatic patients. The presence of de novo mutations, as well as, the presence of mutations with low predicted EA in NC patients reinforces the importance of genotyping for appropriate genetic counseling. In fully genotyped NC patients, the lowest value of ACTH-stimulated 17OHP was 14 ng/ml. Lower cut-off values might overestimate the diagnosis of the NC form.
由于21-羟化酶缺乏导致的先天性肾上腺增生（CAH）是一种可呈现三种临床表型的疾病：两种经典形式——失盐型（SW），残余酶活性（EA）≤1%，以及单纯男性化型（SV），EA为1%-2%，还有一种轻度迟发型或非经典型（NC），EA为10%-60%。我们的目的是描述一组受21-羟化酶缺乏影响的患者的临床特征、生长情况和骨量。此外，对患者及其父母和兄弟姐妹（若有）进行了分子遗传学研究。研究了9例新生儿期诊断的患者和8例青春期前或青春期后诊断的患者。对CYP21A2基因的10个点突变进行了分析。我们发现，除了1例一个等位基因有新发突变R356W的患者外，所有经典表型的患者均通过预测EA<2%的突变进行了全基因分型。5/6的NC患者有高雄激素血症的体征；1例是通过对无症状的兄弟姐妹进行突变检测而确诊的。除1例尚未确定外，所有NC患者均为复合杂合子，一个等位基因携带V281L突变，另一个等位基因预测EA较低。新生儿期诊断的患者在1岁时平均身高较低，不过在青春期开始前有显著增长。我们得出结论，经典型CAH的新生儿期诊断可进行充分的随访以促进生长。对受影响家庭的所有成员进行分子分析可能会发现无症状患者。新发突变的存在以及NC患者中预测EA较低的突变的存在强化了基因分型对于适当遗传咨询的重要性。在全基因分型的NC患者中，促肾上腺皮质激素刺激的17-羟孕酮的最低值为14 ng/ml。更低的临界值可能会高估NC型的诊断。
