Carel J C, Marrakchi Z, Roger M, Morel Y, Chaussain J L
Service d'Endorcrinologie Pédiatrique, Hôpital Saint Vincent de Paul, Paris.
Ann Pediatr (Paris). 1993 Sep;40(7):410-20.
To evaluate the heterogeneity of 21-hydroxylase deficiency with delayed symptoms, clinical and laboratory findings at presentation in 29 patients whose first symptoms occurred after three years of age were analyzed retrospectively. In 12 patients, these data were confronted with the results of molecular CYP21B gene analysis. Age at onset was 7 years on average and was comparable in boys and girls. Premature puberty was the most common presenting symptom [n = 24], whereas hirsutism, clitoral enlargement, and menstruation disorders were less frequent. Six cases were diagnosed as the result of routine studies of family members of index patients. The bone age over statural age ratio was greater than 1 in 19 of the 27 patients. Baseline 17-OH-progesterone levels were elevated in 22 of the 27 patients; magnitude of the elevation varied widely. Levels of 17-OH-progesterone after stimulation with immediate-action tetracosactide were closely correlated with baseline values and established the diagnosis in doubtful cases. Four patients had post-stimulation 17-OH-progesterone levels under 10 ng/ml, suggesting that were heterozygous for the disease. An important finding was that the magnitude of the devation in 17-OH-progesterone was not clearly correlated with clinical findings at presentation (age at onset, growth rate, advance in bone age). Molecular CYP21B gene analysis performed in 12 patients disclosed a homozygous 281 Val Leu mutation in 6 cases. This is the most commonly reported mutation in delayed onset forms. Two patients were heterozygous for the 281 Val Leu mutation and had an allele associated with severe disease, suggesting that the least severely affected chromosome governed clinical presentation of the disease. One boy had an allele associated with neonatal onset on both chromosomes; molecular analysis indicated a risk of antenatal masculinization of female fetuses in this family. This study showed that delayed onset 21-hydroxylase deficiency is a heterogeneous entity and that molecular analysis is essential to genetic counseling.
为评估症状出现延迟的21-羟化酶缺乏症的异质性，对29例首发症状出现在3岁以后的患者就诊时的临床和实验室检查结果进行了回顾性分析。其中12例患者的数据与分子CYP21B基因分析结果进行了对比。发病年龄平均为7岁，男孩和女孩相当。性早熟是最常见的首发症状（n = 24），而多毛症、阴蒂增大和月经紊乱则较少见。6例是对索引患者家庭成员进行常规检查后确诊的。27例患者中有19例骨龄与身高年龄之比大于1。27例患者中有22例基线17-羟孕酮水平升高；升高幅度差异很大。用速效二十四肽促皮质素刺激后17-羟孕酮水平与基线值密切相关，并在可疑病例中确立了诊断。4例患者刺激后17-羟孕酮水平低于10 ng/ml，提示为疾病杂合子。一个重要发现是，17-羟孕酮的偏差幅度与就诊时的临床发现（发病年龄、生长速度、骨龄进展）没有明显相关性。对12例患者进行的分子CYP21B基因分析显示，6例存在纯合的281 Val Leu突变。这是延迟发病形式中最常报道的突变。2例患者为281 Val Leu突变杂合子，且有一个与严重疾病相关的等位基因，提示受影响最轻的染色体决定了疾病的临床表现。1名男孩两条染色体上均有与新生儿发病相关的等位基因；分子分析表明该家族中女性胎儿有产前男性化的风险。本研究表明，迟发性21-羟化酶缺乏症是一种异质性疾病，分子分析对遗传咨询至关重要。
