Chen Chun, Zhou Rui, Fang Yanlan, Jiang Liqiong, Liang Li, Wang Chunlin
Department of Pediatrics, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, China.
Department of Anaesthesia, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, China.
Mol Genet Metab Rep. 2016 Sep 10;9:15-7. doi: 10.1016/j.ymgmr.2016.09.003. eCollection 2016 Dec.
Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disorder in which the adrenal cortex fails to respond appropriately to stimulation by adrenocorticotropic hormone (ACTH) to produce cortisol. The disease is characterized in laboratory testing by glucocorticoid deficiency and markedly elevated ACTH levels. FGD may present in infancy or early childhood with symptoms related to low cortisol and high ACTH, such as hyperpigmentation, severe hypoglycemia, failure to thrive and recurrent infections. Mutations in the MC2R accessory protein (MRAP) cause FGD types 2, which accounts for approximately 15-20% of FGD cases. Here, we report a female neonate of Chinese Han origin, who presented with noted hyperpigmentation at birth. Laboratory investigations revealed hypocortisolaemia (cortisol < 1.0 μg/dl) and elevated plasma ACTH (1051 pg/ml). She responded to hydrocortisone treatment. Genetic studies confirmed the diagnosis showing homozygous deletion (c. 106 + 1delG) in intron 3 of MRAP gene, a mutation already reported as responsible for FDG type 2. This mutation can cause complete lack of ACTH response thus explaining the early presentation in this case. Her parents and maternal grandmother were heterozygous for the same mutation. To our knowledge, this is the first Chinese Han patient reported with FGD type 2 due to a known MRAP mutation.
家族性糖皮质激素缺乏症（FGD）是一种罕见的常染色体隐性疾病，其中肾上腺皮质无法对促肾上腺皮质激素（ACTH）的刺激做出适当反应以产生皮质醇。该疾病在实验室检测中的特征是糖皮质激素缺乏和ACTH水平显著升高。FGD可能在婴儿期或幼儿期出现，伴有与低皮质醇和高ACTH相关的症状，如色素沉着、严重低血糖、生长发育迟缓及反复感染。MC2R辅助蛋白（MRAP）的突变导致2型FGD，约占FGD病例的15% - 20%。在此，我们报告一名中国汉族女新生儿，出生时即有明显色素沉着。实验室检查显示皮质醇血症过低（皮质醇<1.0μg/dl）及血浆ACTH升高（1051pg/ml）。她对氢化可的松治疗有反应。基因研究证实诊断，显示MRAP基因第3内含子存在纯合缺失（c.106 + 1delG），该突变已被报道为导致2型FDG的原因。此突变可导致完全缺乏ACTH反应，从而解释了该病例的早期表现。她的父母和外祖母对此相同突变呈杂合状态。据我们所知，这是首例因已知MRAP突变而报告的中国汉族2型FGD患者。
