Patt Hiren, Koehler Katrin, Lodha Sailesh, Jadhav Swati, Yerawar Chaitanya, Huebner Angela, Thakkar Kunal, Arya Sneha, Nair Sandhya, Goroshi Manjunath, Ganesh Hosahithlu, Sarathi Vijaya, Lila Anurag, Bandgar Tushar, Shah Nalini
Department of EndocrinologySeth G.S. Medical College & KEM Hospital, Mumbai, Maharashtra, India.
Department of PaediatricsUniversity Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Endocr Connect. 2017 Nov;6(8):901-913. doi: 10.1530/EC-17-0255.
To study genotype-phenotype spectrum of triple A syndrome (TAS).
Retrospective chart analysis of Indian TAS patients (cohort 1, = 8) and review of genotyped TAS cases reported in world literature (cohort 2, = 133, 68 publications).
Median age at presentation was 4.75 years (range: 4-10) and 5 years (range: 1-42) for cohorts 1 and 2, respectively. Alacrima, adrenal insufficiency (AI), achalasia and neurological dysfunction (ND) were seen in 8/8, 8/8, 7/8 and 4/8 patients in cohort 1, and in 99, 91, 93 and 79% patients in cohort 2, respectively. In both cohorts, alacrima was present since birth while AI and achalasia manifested before ND. Mineralocorticoid deficiency (MC) was uncommon (absent in cohort 1, 12.5% in cohort 2). In cohort 1, splice-site mutation in exon 1 (p.G14Vfs45) was commonest, followed by a deletion in exon 8 (p.S255Vfs36). Out of 65 mutations in cohort 2, 14 were recurrent and five exhibited regional clustering. AI was more prevalent, more often a presenting feature, and was diagnosed at younger age in T group (those with truncating mutations) as compared to NT (non-truncating mutations) group. ND was more prevalent, more common a presenting feature, with later age at onset in NT as compared to T group.
Clinical profile of our patients is similar to that of patients worldwide. Alacrima is the earliest and most consistent finding. MC deficiency is uncommon. Some recurrent mutations show regional clustering. p.G14Vfs45 and p.S255Vfs36 account for majority of mutations in our cohort. Phenotype of T group differs from that of NT group and merits future research.
研究三A综合征（TAS）的基因型-表型谱。
对印度TAS患者进行回顾性病历分析（队列1，n = 8），并回顾世界文献中报道的基因分型TAS病例（队列2，n = 133，68篇出版物）。
队列1和队列2患者的中位就诊年龄分别为4.75岁（范围：4 - 10岁）和5岁（范围：1 - 42岁）。队列1中8/8、8/8、7/8和4/8的患者出现泪腺缺乏、肾上腺功能不全（AI）、贲门失弛缓症和神经功能障碍（ND），队列2中分别为99%、91%、93%和79%的患者出现上述情况。在两个队列中，泪腺缺乏自出生就存在，而AI和贲门失弛缓症在ND之前出现。盐皮质激素缺乏（MC）不常见（队列1中无，队列2中为12.5%）。在队列1中，外显子1的剪接位点突变（p.G14Vfs45）最常见，其次是外显子8的缺失（p.S255Vfs36）。在队列2的65个突变中，14个是复发性的，5个表现出区域聚集性。与非截断突变（NT）组相比，AI在截断突变（T）组中更普遍，更常作为首发特征，且诊断年龄更小。ND在NT组中更普遍，更常作为首发特征，发病年龄比T组晚。
我们患者的临床特征与全球患者相似。泪腺缺乏是最早且最一致的表现。MC缺乏不常见。一些复发性突变表现出区域聚集性。p.G14Vfs45和p.S255Vfs36占我们队列中突变的大部分。T组的表型与NT组不同，值得未来研究。
