Two siblings with triple A syndrome and novel mutation presenting as hereditary polyneuropathy
Two siblings with triple A syndrome and novel mutation presenting as hereditary polyneuropathy
复制标题
DOI：
10.1007/s00431-010-1314-4
复制
发表时间：
2011-03-01
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
描述了两个兄弟姐妹（女孩3.5岁，男孩5.5岁）的三A综合征的临床和分子数据，早期发作的神经功能障碍。两例患者在儿童早期均表现出发育里程碑延迟和神经功能障碍（运动和感觉脱髓鞘性神经病、明显反射亢进、小腿萎缩、高弓足、步态障碍），被误诊为遗传性多发性神经病，最有可能是腓骨肌萎缩症。在3岁的妹妹出现严重的肾上腺危象后，对5.5岁的哥哥进行了评估，发现了潜在的肾上腺功能不全。由于兄弟姐妹都有泪流满面、手掌角化过度、鹅毛皮肤和鼻音，因此考虑诊断为三A综合征。AAAS基因测序检测到一个复合杂合突变，包括外显子9的新突变p.Ser296Tyr（c.887C > A）和先前描述的外显子8的p.Ser263Pro（c.787T > C）错义突变。总之，在出现早期神经功能障碍和发育迟缓的患者中，应考虑三A综合征。泪点是最早出现和最一致的临床体征，应采用Schirmer试验进行检查。患者应定期检查肾上腺功能障碍，以防止危及生命的肾上腺危象。
The clinical and molecular data on triple A syndrome in two siblings (girl 3.5 years and boy 5.5 years at presentation) with early onset of neurological dysfunction are described. Both patients showed delayed developmental milestones and neurological dysfunctions (motor and sensory demyelinating neuropathy, marked hyperreflexia, calves hypothrophy, pes cavus, gait disturbance) in early childhood, when erroneously diagnosed with hereditary polyneuropathy, most likely Charcot-Marie-Tooth disease. After a severe adrenal crisis in the younger sister at the age of 3 years, the older brother aged 5.5 years was also evaluated and latent adrenal insufficiency was discovered. As both of the siblings had alacrima, hyperkeratosis of palms, cutis anserina, and nasal speech, diagnosis of triple A syndrome was considered. Sequencing of the AAAS gene detected a compound heterozygous mutation consisting of a novel mutation p.Ser296Tyr (c.887C > A) in exon 9 and a previously described p.Ser263Pro (c.787T > C) missense mutation in exon 8 in both siblings. In conclusion, triple A syndrome should be considered in patients presenting with early neurological dysfunction and developmental delay. Alacrima as the earliest and most consistent clinical sign should be investigated by Schirmer test. Patients should be regularly tested for adrenal dysfunction to prevent life-threatening adrenal crises.