Eunice Kennedy Shriver National Institute of Child Health and Human Development, 10 Center Drive, Building 10, Room 1-3330, Bethesda, MD, 20892, USA.
Hormones (Athens). 2019 Mar;18(1):109-112. doi: 10.1007/s42000-018-0089-2. Epub 2019 Jan 5.
Triple A syndrome is a rare autosomal recessive disorder caused by mutations in the AAAS gene on chromosome 12q13. Its main clinical features are alacrima, achalasia, and adrenal insufficiency, with most patients also having neurological symptoms and autonomic dysfunction. The neurologic manifestations are less well-understood, especially in children. Here, we examine two siblings who were found to have a novel mutation in the AAAS gene and who were found to have subtle, but important, neurologic findings.
This is a case report of two siblings.
We discuss two siblings exhibiting different signs of the disorder including neurologic dysfunction found at varying ages. Genetic analysis revealed that both patients have the same compound heterozygous mutations in the AAAS gene consisting of one novel mutation (c.500 C>A, A167E) and one previously described mutation (c.1331+1G> A/IVS14+1 G>A). A diagnosis of triple A syndrome was reached based on their clinical and genetic findings.
The unique characteristic of these two cases is the novel mutation in the AAAS gene, which is likely pathogenic. In addition, they showcase the genotype-phenotype variability of the disease, as well as the importance of early identification of the neurologic abnormalities, which can result in early intervention and possibly improved outcomes.
三重 A 综合征是一种罕见的常染色体隐性遗传病，由 12q13 染色体上的 AAAS 基因突变引起。其主要临床特征为眼干、食管失弛缓症和肾上腺皮质功能不全，大多数患者还伴有神经症状和自主神经功能障碍。神经表现的了解较少，尤其是在儿童中。在这里，我们研究了两个兄弟姐妹，他们在 AAAS 基因中发现了一个新的突变，并且发现了微妙但重要的神经学发现。
这是一个关于两个兄弟姐妹的病例报告。
我们讨论了两个表现出不同疾病迹象的兄弟姐妹，包括在不同年龄发现的神经功能障碍。遗传分析显示，两名患者均在 AAAS 基因中具有相同的复合杂合突变，包括一个新的突变（c.500 C>A，A167E）和一个以前描述的突变（c.1331+1G> A/IVS14+1 G>A）。根据他们的临床和遗传发现，诊断为三重 A 综合征。
这两个病例的独特特征是 AAAS 基因中的新突变，这可能是致病的。此外，它们展示了疾病的基因型-表型变异性，以及早期识别神经异常的重要性，这可以导致早期干预，并可能改善结局。
