Pediatric Endocrinology Division Children's Hospital, University of Bonn, Adenauerallee, 119 53113, Bonn, Germany.
Pediatric Endocrinology Division, Children's Hospital, University of Kiel, Kiel, Germany.
BMC Endocr Disord. 2019 Oct 30;19(1):116. doi: 10.1186/s12902-019-0448-2.
We report a novel mutation within the StAR gene, causing congenital adrenal hyperplasia, with the so far unreported association with heterochromia iridis.
In a now 15-year-old girl (born at 41 + 6 weeks of gestation) adrenal failure was diagnosed in the neonatal period based on the clinical picture with spontaneous hypoglycaemia, hyponatremia and an extremely elevated concentration of ACTH (3381 pmol/l; ref. level 1,1-10,1 pmol/l), elevated renin (836 ng/l; ref. level 5-308 ng/l), and a decreased concentration of aldosterone (410 pmol/l; ref. level 886-3540 pmol/l). In addition to hyperpigmented skin the patient exhibited sectorial heterochromia iridis. Sequence analysis of the steroidogenic acute regulatory protein (StAR) gene showed a novel homozygous mutation (c.652G > A (p.Ala218Thr), which was predicted in-silico to be possibly damaging. Under daily steroid substitution her electrolyte levels are balanced while she became obese. Puberty occurred spontaneously.
A novel mutation in the StAR gene was identified in a patient with severe adrenal hypoplasia and sectorial heterochromia iridis. We discuss a causal relationship between these two rare phenotypes, i.e. whether very high levels of ACTH and alpha-MSH during early development might have disturbed early differentiation and distribution of uveal melanocytes. If confirmed in additional cases, discolorization of the iris might be considered as an additional phenotypical feature in the differential diagnosis of congenital adrenal insufficiency.
我们报道了一个 StAR 基因突变导致先天性肾上腺增生的病例，该突变与虹膜异色症有关，这是目前尚未报道过的。
患者为一名 15 岁女孩，（胎龄 41+6 周时）出生，新生儿期因自发性低血糖、低钠血症和极高的促肾上腺皮质激素（ACTH）浓度（3381 pmol/l；参考水平 1,1-10,1 pmol/l）、高肾素（836 ng/l；参考水平 5-308 ng/l）和低醛固酮（410 pmol/l；参考水平 886-3540 pmol/l）而被诊断为肾上腺功能衰竭。除了色素沉着过度的皮肤外，患者还表现出扇形虹膜异色症。类固醇生成急性调节蛋白（StAR）基因突变分析显示存在一种新的纯合突变（c.652G>A（p.Ala218Thr），这在计算机预测中被认为可能是有害的。在每日激素替代治疗下，她的电解质水平保持平衡，同时她变得肥胖。青春期自发发生。
在一名严重肾上腺发育不全和扇形虹膜异色症患者中发现了 StAR 基因的新突变。我们讨论了这两种罕见表型之间的因果关系，即早期发育过程中 ACTH 和 alpha-MSH 的非常高水平是否可能干扰了葡萄膜黑色素细胞的早期分化和分布。如果在其他病例中得到证实，虹膜变色可能被认为是先天性肾上腺功能不全鉴别诊断中的另一个表型特征。
