Abstract：
Asparagine synthetase deficiency (ASNSD) is a rare neurometabolic disease. Patients may not demonstrate low asparagine levels, which highlights the advantage of molecular over biochemical testing in the initial work-up of ASNSD. We aimed to further delineate the ASNSD variant and phenotypic spectrum and determine the value of biochemical testing as a frontline investigation in ASNSD.
We retrospectively collected the clinical and molecular information on 13 families with ASNSD from the major metabolic clinics in Saudi Arabia.
The major phenotypes included congenital microcephaly (100%), facial dysmorphism (100%), global developmental delay (100%), brain abnormalities (100%), spasticity (86%), and infantile-onset seizures (93%). Additional unreported phenotypes included umbilical hernia, osteopenia, eczema, lung hypoplasia, and hearing loss. Overall, seven homozygous variants accounted for ASNSD. The p.Tyr398Cys and p.Asn75Ile variants accounted for 54% of the cases. The clinical sensitivity and specificity of the proposed biochemical analysis of cerebrospinal fluid (CSF) for the detection of patients with ASNSD were 83% and 98%, respectively.
Our study describes the largest reported ASNSD cohort with clinical, molecular, and biochemical characterization. Taking into consideration the suboptimal sensitivity of biochemical screening, the delineation of the phenotype variant spectrum is of diagnostic utility for accurate diagnosis, prognosis, counseling, and carrier screening.
We retrospectively collected the clinical and molecular information on 13 families with ASNSD from the major metabolic clinics in Saudi Arabia.
The major phenotypes included congenital microcephaly (100%), facial dysmorphism (100%), global developmental delay (100%), brain abnormalities (100%), spasticity (86%), and infantile-onset seizures (93%). Additional unreported phenotypes included umbilical hernia, osteopenia, eczema, lung hypoplasia, and hearing loss. Overall, seven homozygous variants accounted for ASNSD. The p.Tyr398Cys and p.Asn75Ile variants accounted for 54% of the cases. The clinical sensitivity and specificity of the proposed biochemical analysis of cerebrospinal fluid (CSF) for the detection of patients with ASNSD were 83% and 98%, respectively.
Our study describes the largest reported ASNSD cohort with clinical, molecular, and biochemical characterization. Taking into consideration the suboptimal sensitivity of biochemical screening, the delineation of the phenotype variant spectrum is of diagnostic utility for accurate diagnosis, prognosis, counseling, and carrier screening.
摘要：
天冬酰胺合成酶缺乏症(ASNSD)是一种罕见的神经代谢疾病。患者可能没有表现出低天冬酰胺水平，这突出了在ASNSD的初始工作中分子比生化测试的优势。我们旨在进一步描述ASNSD变体和表型谱，并确定生化测试作为ASNSD一线研究的价值。
我们回顾性收集了沙特阿拉伯主要代谢诊所的13个ASNSD家族的临床和分子信息。
主要表型包括先天性小头畸形（100％），面部畸形(100%)，全球发育迟缓(100%)，大脑异常（100%），痉挛（86%），和婴儿发作性癫痫(93%)。其他未报告的表型包括脐疝，骨质减少,湿疹,肺发育不全,和听力损失。总的来说,七个纯合变体占ASNSD。p.Tyr398Cys和p.Asn75Ile变体占病例的54%。拟用脑脊液(CSF)生化分析检测ASNSD患者的临床敏感性和特异性分别为83%和98%,分别。
我们的研究描述了最大的ASNSD队列报道，分子，和生化表征。考虑到生化筛查的敏感性欠佳，表型变异谱的描绘对准确诊断具有诊断效用，预后,咨询,和载体筛选。
我们回顾性收集了沙特阿拉伯主要代谢诊所的13个ASNSD家族的临床和分子信息。
主要表型包括先天性小头畸形（100％），面部畸形(100%)，全球发育迟缓(100%)，大脑异常（100%），痉挛（86%），和婴儿发作性癫痫(93%)。其他未报告的表型包括脐疝，骨质减少,湿疹,肺发育不全,和听力损失。总的来说,七个纯合变体占ASNSD。p.Tyr398Cys和p.Asn75Ile变体占病例的54%。拟用脑脊液(CSF)生化分析检测ASNSD患者的临床敏感性和特异性分别为83%和98%,分别。
我们的研究描述了最大的ASNSD队列报道，分子，和生化表征。考虑到生化筛查的敏感性欠佳，表型变异谱的描绘对准确诊断具有诊断效用，预后,咨询,和载体筛选。
