Long-term clinical follow-up and molecular genetic findings in eight patients with triple A syndrome
Long-term clinical follow-up and molecular genetic findings in eight patients with triple A syndrome
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DOI：
10.1007/s00431-012-1745-1
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发表时间：
2012-10-01
影响因子：
3.6
通讯作者：
Huebner, Angela
中科院分区：
文献类型：
--
作者：
Dumic, Miroslav;Barisic, Nina;Huebner, Angela
AAA综合征(Allgrove综合征，OMIM#231550)是由编码核孔蛋白阿拉丁的染色体12q13上的aaas基因的常染色体隐性遗传突变引起的。这种多系统疾病的特征是失弛缓症、软化、肾上腺功能不全和神经功能障碍。我们分析了8例2~35岁AAA综合征患者的长期临床随访和AAAS基因测序结果。在诊断时，所有患者都有软化、神经功能障碍和皮肤病，其中7例伴有肾上腺功能不全，5例伴有失弛缓症。对AAAS基因的测序发现，在8名患者中有5名患者存在p.S263P突变，支持该突变是斯拉夫人的创始人突变的假设。其中1例为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突变和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。随访4~29年，患者病情进展，出现新的症状。这些症状虽然严重，但在所有6名年轻成人患者中出现的许多症状往往被忽视或忽视：体位性低血压伴视力模糊和晕厥，低血压导致完全脱牙，距骨挛缩伴永久性行走困难，以及男性患者的勃起功能障碍。AAA综合征是一种进行性衰弱障碍，可严重影响患者的生活质量，甚至危及严重神经功能障碍患者的生命。结论：对AAA综合征患者的长期随访显示出涉及多个系统的多种临床特征。进行性自然病程可能严重影响患者的生活质量，甚至危及严重神经功能障碍患者的生命。
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. Conclusion: 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.