Introduction

Triple A (Allgrove) syndrome is a rare autosomal recessive disorder characterized by cardinal features of primary adrenal insufficiency (AI) due to adrenocorticotropic hormone (ACTH) resistance, achalasia, and alacrima. It is frequently associated with neurological manifestations such as autonomic dysfunction, cognitive dysfunction, cranial nerve, or motor involvement. Amyotrophy/motor neuron disease is a rare association.

Case presentation

We herein report a 19-year-old boy diagnosed with triple A syndrome (TAS), with the classic triad of ACTH-resistant adrenal insufficiency, achalasia, and alacrima. Additionally, he had distal spinal muscle amyotrophy. Alacrima was the earliest feature evident in early childhood, followed by achalasia at 12 years of age. He was diagnosed with AI at the age of 19 years, with involvement of the mineralocorticoid axis. Further evaluation showed a neurogenic pattern on electromyography, consistent with a diagnosis of motor neuron disease. A nerve conduction study revealed no significant neuropathy. Genetic analysis confirmed a pathogenic homozygous mutation in the AAAS gene c.43C>A, p.Gln15Lys. He improved with glucocorticoid and mineralocorticoid supplements for AI, and nifedipine for achalasia and artificial tears. He is planned for esophagomyotomy.

Conclusion

In any young patient with AI not due to congenital adrenal hyperplasia, Allgrove syndrome should be ruled out. Though mineralocorticoid sparing pattern is classical, it can rarely be involved, as seen in the index case. Various components of the syndrome, as well as amyotrophy and other neurologic features, may present in a metachronous fashion. Hence, a high index of clinical suspicion can aid in early diagnosis and management.

中文翻译：

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AAAS 基因突变导致的 Triple A (Allgrove) 综合征与罕见的肌萎缩相关。

介绍

Triple A (Allgrove) 综合征是一种罕见的常染色体隐性遗传病，其主要特征是由促肾上腺皮质激素 (ACTH) 抵抗、贲门失弛缓症和泪腺症引起的原发性肾上腺皮质功能减退症 (AI)。它经常与神经系统表现有关，例如自主神经功能障碍、认​​知功能障碍、颅神经或运动受累。肌萎缩/运动神经元疾病是一种罕见的关联。

案例展示

我们在此报告一名 19 岁男孩被诊断​​为三联 A 综合征 (TAS)，具有 ACTH 抵抗性肾上腺功能不全、贲门失弛缓症和泪腺炎的经典三联征。此外，他还有远端脊髓肌萎缩症。Alacrima 是儿童早期明显的最早特征，其次是 12 岁时的贲门失弛缓症。他在 19 岁时被诊断为 AI，涉及盐皮质激素轴。进一步评估显示肌电图显示神经源性模式，与运动神经元疾病的诊断一致。一项神经传导研究显示没有明显的神经病变。基因分析证实了AAAS 中的致病纯合突变基因 c.43C>A，p.Gln15Lys。他用糖皮质激素和盐皮质激素补充剂治疗 AI，使用硝苯地平治疗贲门失弛缓症和人工泪液，情况有所改善。他计划进行食管肌切开术。

结论

在任何非先天性肾上腺增生的年轻 AI 患者中，应排除 Allgrove 综合征。尽管盐皮质激素保留模式是经典的，但很少涉及，如索引病例所示。该综合征的各种组成部分，以及肌萎缩和其他神经系统特征，可能以异时方式出现。因此，高度的临床怀疑有助于早期诊断和管理。