EGL Genetic Diagnostics, LLC, Tucker, GA, USA.
Medical Genetics Branch, NHGRI, NIH, Bethesda, MD, USA; Division of Genetic Medicine, Department of Pediatrics, University of Washington School of Medicine, Seattle, WA, USA; Division of Genetic Medicine, Department of Pediatrics, Seattle Children's Hospital, Seattle, WA, USA.
Mol Genet Metab. 2018 May;124(1):82-86. doi: 10.1016/j.ymgme.2018.03.002. Epub 2018 Mar 10.
N-glycanase deficiency (NGLY1 deficiency, NGLY1-CDDG), the first autosomal recessive congenital disorder of N-linked deglycosylation (CDDG), is caused by pathogenic variants in NGLY1. The majority of affected individuals have been identified using exome or genome sequencing. To date, no reliable, clinically available biomarkers have been identified. Urine oligosaccharide analysis was included as part of a routine evaluation for possible biomarkers in patients with confirmed NGLY1-CDDG. During the qualitative review of oligosaccharide profiles by an experienced laboratory director an abnormal analyte with a proposed structure of Neu5Ac1Hex1GlcNAc1-Asn was identified in NGLY1-CDDG patient urine samples. The same species has been observed in profiles from individuals affected with aspartylglucosaminuria, although the complete spectra are not identical. Additional studies using tandem mass spectrometry confirmed the analyte's structure. In addition to the known NGLY1-CDDG patients identified by this analysis, a single case was identified in a population referred for clinical testing who subsequently had a diagnosis of NGLY1-CDDG confirmed by molecular testing. Urine oligosaccharide screening by MALDI-TOF MS can identify individuals with NGLY1-CDDG. In addition, this potential biomarker might also be used to monitor the effectiveness of therapeutic options as they become available.
N-糖基化酶缺乏症（NGLY1 缺乏症，NGLY1-CDDG）是一种由 NGLY1 中的致病变异引起的常染色体隐性先天性 N 连接糖基化脱糖基化（CDDG）障碍，大多数受影响的个体已通过外显子组或基因组测序确定。迄今为止，尚未发现可靠的、临床可用的生物标志物。尿寡糖分析被纳入确诊为 NGLY1-CDDG 患者的可能生物标志物的常规评估中。在经验丰富的实验室主任对寡糖图谱进行定性审查期间，在 NGLY1-CDDG 患者的尿液样本中发现了一种具有 Neu5Ac1Hex1GlcNAc1-Asn 结构的异常分析物。在患有天冬氨酸葡糖胺尿症的个体的图谱中观察到了相同的物质，尽管完整的图谱并不完全相同。使用串联质谱法的进一步研究证实了分析物的结构。除了通过该分析确定的已知 NGLY1-CDDG 患者外，在接受临床检测的人群中还发现了一个单独的病例，随后通过分子检测证实该病例患有 NGLY1-CDDG。MALDI-TOF MS 尿寡糖筛选可识别 NGLY1-CDDG 个体。此外，这种潜在的生物标志物也可用于监测治疗选择的有效性，因为它们会变得可用。
