Gerards Judith, Ritter Michael M, Kaminsky Elke, Gal Andreas, Hoeppner Wolfgang, Quinkler Marcus
Endocrinology in Charlottenburg.
Diabetology and Endocrinology, HELIOS Klinikum Berlin-Buch, Berlin, Germany.
Endocrinol Diabetes Metab Case Rep. 2017 Sep 4;2017. doi: 10.1530/EDM-17-0054. eCollection 2017.
DAX1 (NR0B1) is an orphan nuclear receptor, which plays an important role in development and function of the adrenal glands and gonads. Mutations in DAX1 cause X-linked adrenal hypoplasia congenita (X-linked AHC), which is characterized by adrenal insufficiency (AI) and hypogonadotropic hypogonadism (HHG). Affected boys present with adrenal failure usually in childhood and, later in life, with delayed puberty. However, patients with a late-onset form of X-linked AHC have also been described in the past years. We report a male patient who presented with symptoms of an adrenal crisis at the age of 38 years and was later diagnosed with HHG. Family history was positive with several male relatives diagnosed with AI and compatible with the assumed X-chromosomal inheritance of the trait. Direct sequencing of DAX1 of the patient revealed a hemizygous cytosine-to-thymine substitution at nucleotide 64 in exon 1, which creates a novel nonsense mutation (p.(Gln22*)). In order to compare the clinical presentation of the patient to that of other patients with X-linked AHC, we searched the electronic database MEDLINE (PubMed) and found reports of nine other cases with delayed onset of X-linked AHC. In certain cases, genotype-phenotype correlation could be assumed.
X-linked AHC is a rare disease characterized by primary AI and hypogonadotropic hypogonadism (HHG). The full-blown clinical picture is seen usually only in males with a typical onset in childhood.Patients with a late-onset form of X-linked AHC have also been described recently. Being aware of this late-onset form might help to reach an early diagnosis and prevent life-threatening adrenal crises.Adult men with primary AI of unknown etiology should be investigated for HHG. Detecting a DAX1 mutation may confirm the clinical diagnosis of late-onset X-linked AHC.In relatives of patients with genetically confirmed X-linked AHC, targeted mutation analysis may help to identify family members at risk and asymptomatic carriers, and discuss conscious family planning.
DAX1（NR0B1）是一种孤儿核受体，在肾上腺和性腺的发育及功能中起重要作用。DAX1突变会导致X连锁先天性肾上腺发育不全（X连锁AHC），其特征为肾上腺功能不全（AI）和低促性腺激素性性腺功能减退（HHG）。受影响的男孩通常在儿童期出现肾上腺功能衰竭，在成年后出现青春期延迟。然而，过去几年也有迟发型X连锁AHC患者的报道。我们报告一名38岁男性患者，其出现肾上腺危象症状，后来被诊断为HHG。家族史呈阳性，有几名男性亲属被诊断为AI，符合该性状假定的X染色体遗传。对患者的DAX1进行直接测序，发现外显子1中第64位核苷酸处存在半合子胞嘧啶到胸腺嘧啶的替换，产生了一个新的无义突变（p.(Gln22*)）。为了将该患者的临床表现与其他X连锁AHC患者进行比较，我们检索了电子数据库MEDLINE（PubMed），发现了另外9例迟发型X连锁AHC病例的报告。在某些情况下，可以假定基因型与表型的相关性。
X连锁AHC是一种罕见疾病，其特征为原发性AI和低促性腺激素性性腺功能减退（HHG）。通常只有在儿童期典型发病男性中才会出现全面的临床表现。最近也有迟发型X连锁AHC患者的报道。了解这种迟发型形式可能有助于早期诊断并预防危及生命的肾上腺危象。病因不明的原发性AI成年男性应进行HHG检查。检测到DAX1突变可确诊迟发型X连锁AHC的临床诊断。在基因确诊的X连锁AHC患者的亲属中，靶向突变分析可能有助于识别有风险的家庭成员和无症状携带者，并讨论有意识的计划生育。
