PRPS1基因,位于Xq22.3上,编码磷酸核糖焦磷酸合成酶(PRPS),嘌呤从头合成的关键酶。三种临床表型与功能丧失的PRPS1变异和降低的PRPS活性相关:艺术综合征(OMIM:301835),Charcot-Marie-Tooth疾病5型(CMTX5,OMIM:311070),和非综合征性X连锁耳聋(DFN2,OMIM:304500)。听力损失在所有情况下都存在。CMTX5患者还表现出周围神经病变和视神经萎缩。艺术综合征包括发育迟缓,智力残疾,共济失调,和对感染的易感性,除了以上三个特点。功能增益PRPS1变体导致具有高尿酸血症和痛风的PRPS超活性(OMIM:300661)。我们报告了一个6岁的男孩,他表现出明显的全身性肌张力减退,全球发育迟缓,缺乏言语,树干不稳定,锻炼不容忍,张着嘴的低反应脸,口咽吞咽困难,构音障碍,和频繁的上呼吸道感染。然而,他的神经传导速度,听力学,眼底检查是正常的。一种新颖的半合子变体,c.130A>Gp.(Ile44Val),通过面板测序在PRPS1基因中发现。红细胞中的PRPS活性明显降低,确认变异体的致病性。血清尿酸、尿嘌呤和嘧啶代谢物水平均正常。总之,我们提出了一个新的PRPS1功能丧失变异的病人有一些临床特征的艺术综合征,但是缺乏一个主要的属性,听力损失,在所有其他报道的Arts综合征患者中,这是先天性/早发性。此外,重要的是要承认血清和尿嘌呤和嘧啶代谢物的正常水平不能排除PRPS1相关疾病.
The
PRPS1 gene, located on Xq22.3, encodes phosphoribosyl-pyrophosphate synthetase (PRPS), a key enzyme in de novo purine synthesis. Three clinical phenotypes are associated with loss-of-function
PRPS1 variants and decreased PRPS activity: Arts syndrome (OMIM: 301835), Charcot-Marie-Tooth disease type 5 (CMTX5, OMIM: 311070), and nonsyndromic X-linked deafness (DFN2, OMIM: 304500). Hearing loss is present in all cases. CMTX5 patients also show peripheral neuropathy and optic atrophy. Arts syndrome includes developmental delay, intellectual disability, ataxia, and susceptibility to infections, in addition to the above three features. Gain-of-function
PRPS1 variants result in PRPS superactivity (OMIM: 300661) with hyperuricemia and gout. We report a 6-year-old boy who presented with marked generalized muscular hypotonia, global developmental delay, lack of speech, trunk instability, exercise intolerance, hypomimic face with open mouth, oropharyngeal dysphagia, dysarthria, and frequent upper respiratory tract infections. However, his nerve conduction velocity, audiologic, and funduscopic investigations were normal. A novel hemizygous variant, c.130A > G p.(Ile44Val), was found in the
PRPS1 gene by panel sequencing. PRPS activity in erythrocytes was markedly reduced, confirming the pathogenicity of the variant. Serum uric acid and urinary purine and pyrimidine metabolite levels were normal. In conclusion, we present a novel
PRPS1 loss-of-function variant in a patient with some clinical features of Arts syndrome, but lacking a major attribute, hearing loss, which is congenital/early-onset in all other reported Arts syndrome patients. In addition, it is important to acknowledge that normal levels of serum and urinary purine and pyrimidine metabolites do not exclude PRPS1-related disorders.