5-Aminolevulinic acid can ameliorate language dysfunction of patients with ATR-X syndrome.
5-Aminolevulinic acid can ameliorate language dysfunction of patients with ATR-X syndrome.
复制标题
5-氨基乙酰丙酸可以改善ATR-X综合征患者的语言功能障碍。
DOI：
10.1111/cga.12365
复制
发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Shioda N.
中科院分区：
文献类型：
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作者：
Wada T;Suzuki S;Shioda N.
ATR-X综合征(OMIM#301040)是一种由ATRX基因突变引起的X连锁智能障碍综合征，以男性患者、严重的智能障碍、特征性的中枢性低张相、α-地中海贫血、骨骼、生殖器和消化异常以及自闭症行为为特征。1基于这些临床特征，包括α-珠蛋白基因在内的许多基因的表达在ATR-X患者中应该受到干扰。ATRX蛋白针对串联重复序列，形成鸟嘌呤四链(G4)结构，并调节附近的基因。2我们最近报道了5-氨基乙酰丙酸(5-ALA)，它可以改善ATR-X模型小鼠的认知功能，是一种潜在的靶向G-四联体的治疗策略。3这是第一例ATR-X综合征男孩的病例报告，他的语言能力在服用5-ALA后有所改善。该病例是一名5岁6个月大的男婴，他被诊断为ATR-X综合征，ATRX基因有一个无意义的变异；NM_000489。5(ATRX)：C.7192C>；T，第Gln2398页*。他的堂兄也被诊断为ATR-X综合征，带有相同的ATRX突变。出生时37周无窒息(体重3172g，身高51 cm，头围42.5 cm)。他的运动发育被推迟了，31个月时他开始在没有支撑的情况下走路。他具有ATR-X综合征的典型临床特征，包括严重的智力残疾、发育迟缓、中枢低张相、反复呕吐、便秘、隐睾症和睾丸未降。他的脑部核磁共振成像显示痂状体发育不全。在3岁零4个月的时候，他不会说任何有意义的话。他的父亲开始给他口服5-丙氨酸一次5-氨基乙酰丙酸
ATR-X syndrome (OMIM# 301040) is one of the X-linked intellectual disability syndromes caused by mutations in the ATRX gene, characterized by male patients, severe intellectual disability, characteristic central hypotonic facies, α-thalassemia (HbH), skeletal, genital, and digestive abnormalities, and autistic behavior. 1 Based on these clinical features, the expression of many genes, including the α-globin gene, should to be disturbed in ATR-X patients. The ATRX protein targets tandem repeats, forming guanine-quadruplex (G4) structures, and regulates nearby genes. 2 We have recently reported that 5-aminolevulinic acid (5-ALA), can be a potential therapeutic strategy to target G-quadruplexes as it improved cognitive function in ATR-X model mice. 3 This is the first case report of a boy with ATR-X syndrome, whose language ability has been improving since taking 5-ALA. The case is a5-year-6-month-old boy, who was diagnosed as ATR-X syndrome with a nonsense variant in ATRX gene; NM_000489. 5 (ATRX): c. 7192C> T, p. Gln2398*. His cousin is also diagnosed as ATR-X syndrome with the same ATRX mutation. He was born without asphyxia at 37 weeks gestational age (weight: 3172 g, height: 51 cm, head circumference: 42.5 cm). His motor development was delayed and he started walking without support at 31 months. He has characteristic clinical features of ATR-X syndromes, including severe intellectual disability, failure to thrive, central hypotonic facies, recurrent vomiting, constipation, cryptorchidism, and undescended testis. His brain magnetic resonance imaging shows hypoplasia of the corpus callosum. At the age of 3 years and 4 months, he could not speak any meaningful words. His father started to give him 5-ALA orally once5-aminolevulinic acid