BACKGROUND Allgrove syndrome (OMIM 231550) is a rare autosomal recessive disease characterized by non-CAH primary adrenal insufficiency (non-CAH PAI), alacrima, and achalasia. It is caused by mutations in the AAAS gene. The syndrome is also associated with variable progressive neurological impairment and dermatological abnormalities. METHODS AND RESULTS We diagnosed 23 patients from 14 families with Allgrove syndrome, based on the presence of at least two characteristic symptoms, usually adrenal insufficiency and alacrima, between 2008 and 2018. A previously described nonsense variant of AAAS was detected in 19 patients from 12 families at homozygous state. Another novel homozygous mutation (c.394-397delCTGT) in AAAS was detected in four patients from two families. Presenting symptoms were alacrima (23/23; 100%), adrenal insufficiency (18/23; 78%), achalasia (13/23; 57%), short stature/growth retardation (16/23; 70%), hyperreflexia (15/23; 65%), palmoplantar hyperkeratosis (13/23; 57%), hyperpigmentation of the skin (10/23; 43%), hypoglycemia-induced convulsion (7/23; 30%), swallowing difficulty and vomiting (6/23; 26%). Serum DHEAS concentrations were low in all patients (23/23; 100%). CONCLUSIONS Clinical symptoms vary even among patients carrying the same mutation. Triple A syndrome should be considered in the etiology of non-CAH PAI in Arab populations and in Southeast Turkey. Any child with non-CAH PAI should be evaluated for the presence of alacrima and/or achalasia or family history of alacrima and/or achalasia. Children with alacrima and/or achalasia should also be investigated for adrenal insufficiency. Definitive molecular diagnosis is essential for early diagnosis and management of adrenal insufficiency, neurological symptoms, and growth retardation in patients and early diagnosis of as yet asymptomatic cases in the family, together with genetic counseling.

中文翻译：

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Allgrove综合征的症状范围很广：在安纳托利亚东南部的单中心经验。

背景技术Allgrove综合征（OMIM 231550）是一种罕见的常染色体隐性遗传疾病，其特征在于非CAH原发性肾上腺皮质功能不全（non-CAH PAI），睑板腺和门失弛缓。它是由AAAS基因突变引起的。该综合征还与可变的进行性神经损伤和皮肤病学异常有关。方法和结果我们基于2008年至2018年之间至少存在两种​​特征性症状（通常是肾上腺功能不全和红斑痤疮），诊断了14个家庭的24例Allgrove综合征患者。在先前描述的AAAS变异中，有12例来自19个患者纯合状态的家庭。在来自两个家庭的四名患者中发现了AAAS中的另一个新的纯合突变（c.394-397delCTGT）。呈现的症状为头癣（23/23； 100％），肾上腺功能不全（18/23；78％），门失弛缓症（13/23; 57％），身材/生长迟缓（16/23; 70％），反射亢进（15/23; 65％），掌plant角化过度（13/23; 57％），色素沉着过度皮肤（10/23; 43％），低血糖引起的抽搐（7/23; 30％），吞咽困难和呕吐（6/23; 26％）。所有患者的血清DHEAS浓度均较低（23/23； 100％）。结论即使在携带相同突变的患者中，临床症状也会有所不同。在非CAH PAI的阿拉伯人群和土耳其东南部的病因中应考虑使用Triple A综合征。任何患有非CAH PAI的儿童都应评估是否存在疮和/或门失弛缓症或有cri疮和/或门失弛缓症的家族史。患有泪溢和/或失弛缓症的儿童也应接受肾上腺功能不全的检查。