Araújo Vitor Guilherme Brito de, Oliveira Renata Santarem de, Gameleira Kallianna Paula Duarte, Cruz Cátia Barbosa, Lofrano-Porto Adriana
Molecular Pharmacology Laboratory, Faculty of Health Sciences, University of Brasilia, Brasilia, DF, Brazil.
Genetics Unit, Hospital de Apoio de Brasilia, Brasilia, DF, Brazil.
Arq Bras Endocrinol Metabol. 2014 Aug;58(6):650-5. doi: 10.1590/0004-2730000003098.
3β-hydroxysteroid dehydrogenase II (3β-HSD) deficiency represents a rare CAH variant. Newborns affected with its classic form have salt wasting in early infancy and genital ambiguity in both sexes. High levels of 17-hydroxypregnenolone (Δ517OHP) are characteristic, but extra-adrenal conversion to 17-hydroxyprogesterone (17OHP) may lead to positive results on newborn screening tests. Filter paper 17OHP on newborn screening test was performed by immunofluorometric assay, and serum determinations of 17OHP and Δ517OHP, by radioimmunoassay. A 46,XY infant with genital ambiguity and adrenal crisis at three months of age presented a positive result on newborn screening for CAH. Serum determinations of 17OHP and Δ517OHP were elevated, and a high Δ517OHP/cortisol relation was compatible with the diagnosis of 3β-HSD deficiency. Molecular analysis of the HSD3B2 gene from the affected case revealed the presence of the homozygous p.P222Q mutation, whereas his parents were heterozygous for it. We present the first report of 3β-HSD type II deficiency genotype-proven detected at the Newborn Screening Program in Brazil. The case described herein corroborates the strong genotype-phenotype correlation associated with the HSD3B2 p.P222Q mutation, which leads to a classic salt-wasting 3β-HSD deficiency. Further evaluation of 17OHP assays used in newborn screening tests would aid in determining their reproducibility, as well as the potential significance of moderately elevated 17OHP levels as an early indicator to the diagnosis of other forms of classic CAH, beyond 21-hydroxylase deficiency.
3β-羟基类固醇脱氢酶II（3β-HSD）缺乏症是一种罕见的先天性肾上腺皮质增生症（CAH）变异型。患其经典型的新生儿在婴儿早期会出现失盐症状，且男女两性均有生殖器模糊不清的情况。高水平的17-羟孕烯醇酮（Δ5 17OHP）是其特征，但肾上腺外转化为17-羟孕酮（17OHP）可能导致新生儿筛查试验结果呈阳性。新生儿筛查试验中的滤纸17OHP采用免疫荧光分析法进行检测，血清17OHP和Δ5 17OHP的测定则采用放射免疫分析法。一名46,XY型婴儿在3个月大时出现生殖器模糊和肾上腺危象，新生儿CAH筛查结果呈阳性。血清17OHP和Δ5 17OHP测定值升高，且高Δ5 17OHP/皮质醇比值与3β-HSD缺乏症的诊断相符。对该患病病例的HSD3B2基因进行分子分析，发现存在纯合子p.P222Q突变，而其父母为该突变的杂合子。我们首次报告了在巴西新生儿筛查项目中经基因分型证实的II型3β-HSD缺乏症。本文所述病例证实了与HSD3B2 p.P222Q突变相关的强基因型-表型相关性，该突变导致典型的失盐型3β-HSD缺乏症。进一步评估新生儿筛查试验中使用的17OHP检测方法，将有助于确定其可重复性，以及17OHP水平适度升高作为21-羟化酶缺乏症以外其他形式经典CAH早期诊断指标的潜在意义。
