Nowak Zuzanna, Preizner-Rzucidło Ewelina, Gawlik Jakub, Starzyk Jerzy B, Januś Dominika
Hospital of the Brothers Hospitallers of Saint John of God, 31-061 Krakow, Poland.
Department of Pediatric and Adolescent Endocrinology, Institute of Pediatrics, Jagiellonian University Medical College, 30-663 Krakow, Poland.
Children (Basel). 2024 Oct 12;11(10):1231. doi: 10.3390/children11101231.
Congenital adrenal hyperplasia (CAH) is a group of genetic disorders that lead to the dysfunction of the steroidogenesis pathway, resulting in steroid hormone deficiency of varied intensity. The cholesterol side-chain cleavage enzyme (P450scc), coded by the gene, is vital to the first step in the biosynthesis of steroid hormones, which is the conversion of cholesterol to pregnenolone. Therefore, its deficiency causes a general steroid hormone shortage.
We report a case of CAH caused by P450scc deficiency with complete 46, XY sex reversal, characteristic facial features (narrow middle section of the face, small ears with thick helix, fleshy upturned lobules), and dysmorphic macrocephaly along with shortened upper and lower extremities.
Our patient carries a compound heterozygotic pathogenic variant of the gene, with two frameshift pathogenic variants NM_000781.3():c.358del (p.Arg120Aspfs18) in exon 2 and NM_000781.3():c.835del (p.Ile279Tyrfs10) in exon 5. To date, only around 50 cases with pathogenic variants have been reported worldwide. We believe this is the first described case of a newborn with severe, classic P450scc deficiency in Poland.
CYP11A1 (P450scc) deficiency is a rare and complex disorder that leads to primary adrenal insufficiency and may present with 46, XY disorders of sex development (DSD), phenotypic variations, and associated endocrinological abnormalities. This case, along with others cited, highlights the diverse presentations of DSD in individuals with pathogenic variants. Optimal management necessitates a multidisciplinary approach by a specialized DSD team. Gonadectomy is a key consideration to decrease the teratogenic risk associated with intra-abdominal gonadal tissue.
先天性肾上腺皮质增生症（CAH）是一组遗传性疾病，可导致类固醇生成途径功能障碍，进而导致不同程度的类固醇激素缺乏。由该基因编码的胆固醇侧链裂解酶（P450scc）对于类固醇激素生物合成的第一步至关重要，即胆固醇转化为孕烯醇酮。因此，其缺乏会导致全身性类固醇激素短缺。
我们报告一例由P450scc缺乏引起的CAH病例，该病例伴有完全性46，XY性反转、特征性面部特征（面部中部狭窄、耳朵小且螺旋增厚、耳垂肉质上翘）、大头畸形以及上下肢缩短。
我们的患者携带该基因的复合杂合致病性变异，外显子2中有两个移码致病性变异NM_000781.3():c.358del（p.Arg120Aspfs18），外显子5中有NM_000781.3():c.835del（p.Ile279Tyrfs10）。迄今为止，全球仅报道了约50例具有该致病性变异的病例。我们认为这是波兰首例报道的患有严重经典P450scc缺乏症的新生儿病例。
CYP11A1（P450scc）缺乏是一种罕见且复杂的疾病，可导致原发性肾上腺功能不全，并可能伴有46，XY性发育障碍（DSD）、表型变异以及相关的内分泌异常。该病例以及其他引用病例凸显了携带致病性变异个体中DSD的多种表现形式。最佳管理需要由专业的DSD团队采取多学科方法。性腺切除术是降低与腹腔内性腺组织相关致畸风险的关键考虑因素。
