Division of Endocrinology, Department of Pediatrics, University Hospital Centre Zagreb, Kišpatićeva 12, 10000 Zagreb, Croatia.
Eur J Pediatr. 2012 Oct;171(10):1453-9. doi: 10.1007/s00431-012-1745-1. Epub 2012 Apr 28.
The triple A syndrome (Allgrove syndrome, OMIM #231550) is caused by autosomal recessively inherited mutations in the AAAS gene on chromosome 12q13 encoding the nuclear pore protein ALADIN. This multisystemic disease is characterised by achalasia, alacrima, adrenal insufficiency and neurological impairment. We analyse long-term clinical follow-up and results of sequencing of the AAAS gene in eight patients with triple A syndrome aged from 2 to 35 years. At the time of diagnosis, all patients presented with alacrima, neurological dysfunction, dermatological abnormalities, seven of them with adrenal insufficiency and five of them with achalasia. Sequencing of the AAAS gene identified the p.S263P mutation in five of eight patients, supporting the hypothesis that this mutation is a founder mutation in Slavic population. One of the patients is homozygous for the p.S263P mutation, two are compound heterozygous for the p.S263P and the p.G14fs mutation, two are compound heterozygous for the p.S263Pro mutation and p.S296Y mutation, two are compound heterozygous for the p.G14fs and the p.Q387X mutations and one is homozygous for the p.Q387X mutation. In the course of the follow-up time of 4-29 years, progression of existing and appearance of new symptoms developed. Although severe, many of these symptoms presented in all six young adult patients are often overlooked or neglected: postural hypotension with blurred vision and syncope, hyposalivation resulting with complete edentulosis, talocrular contractures with permanent walking difficulties and erectile dysfunction in male patients. Triple A syndrome is a progressive debilitating disorder which may seriously affect quality of life and even be life-threatening in patients with severe neurological impairment.
Long-term follow-up of patients with triple A syndrome revealed a variety of the clinical features involving many systems. Progressive natural course of the disease may seriously affect quality of life and even be life-threatening in patients with severe neurological impairment.
三重 A 综合征（Allgrove 综合征，OMIM#231550）是由常染色体隐性遗传突变引起的，突变基因位于 12q13 染色体上，编码核孔蛋白 ALADIN。这种多系统疾病的特征是贲门失弛缓症、眼干、肾上腺皮质功能不全和神经功能障碍。我们分析了 8 例年龄在 2 至 35 岁的三重 A 综合征患者的长期临床随访和 AAAS 基因测序结果。在诊断时，所有患者均表现为眼干、神经功能障碍、皮肤异常，其中 7 例伴有肾上腺皮质功能不全，5 例伴有贲门失弛缓症。AAAS 基因测序发现 8 例患者中有 5 例存在 p.S263P 突变，这支持了该突变是斯拉夫人群中的一个创始突变的假说。其中 1 例患者为 p.S263P 突变纯合子，2 例为 p.S263P 和 p.G14fs 突变复合杂合子，2 例为 p.S263Pro 和 p.S296Y 突变复合杂合子，2 例为 p.G14fs 和 p.Q387X 突变复合杂合子，1 例为 p.Q387X 突变纯合子。在 4 至 29 年的随访期间，出现了现有症状的进展和新症状的出现。尽管病情严重，但许多这些症状在所有 6 例年轻成年患者中经常被忽视：体位性低血压伴视力模糊和晕厥、唾液分泌减少导致完全无牙、距跟关节挛缩导致永久性行走困难和男性患者勃起功能障碍。三重 A 综合征是一种进行性衰弱性疾病，在严重神经功能障碍的患者中，可能严重影响生活质量甚至危及生命。
对三重 A 综合征患者的长期随访显示出多种涉及多个系统的临床表现。疾病的进行性自然病程可能严重影响生活质量，甚至在严重神经功能障碍的患者中危及生命。
