Yamamoto Toshiyuki, Shimojima Keiko, Matsufuji Mayumi, Mashima Ryuichi, Sakai Eri, Okuyama Torayuki
Institute of Medical Genetics, Tokyo Women's Medical University, Tokyo, Japan; Institute for Integrated Medical Sciences, Tokyo Women's Medical University, Tokyo, Japan.
Institute of Medical Genetics, Tokyo Women's Medical University, Tokyo, Japan; Institute for Integrated Medical Sciences, Tokyo Women's Medical University, Tokyo, Japan.
Brain Dev. 2017 May;39(5):422-425. doi: 10.1016/j.braindev.2016.12.004. Epub 2017 Jan 4.
Aspartylglucosaminuria (AGU) is an autosomal recessive lysosomal storage disorder caused by a deficiency of the lysosomal enzyme, aspartylglucosaminidase (AGA). This disorder is rare in the general population except in Finland. Since the most characteristic feature of this disorder is a progressive developmental regression, patients often show no specific symptoms in the initial stages, and thus early diagnosis is often challenging.
We encountered a 16-year-old boy who began to show difficulties in his speech at the age of 6years. Due to a mild regression in his development, he gradually lost common daily abilities. His diagnosis was first obtained through exome sequencing that identified a novel homozygous mutation in the AGA gene. This result was reasonable because of parental consanguinity. Reduced enzymatic activity of AGA was then confirmed. His urine was retrospectively screened by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and a specific pattern of abnormal metabolites was identified.
Because both exome sequencing and MALDI-TOF-MS screening are adaptable and comprehensive, future combinatory use of these methods would be useful for diagnosis of rare inborn errors of metabolism such as AGU.
天冬氨酰氨基葡糖苷酶缺乏症（AGU）是一种常染色体隐性溶酶体贮积症，由溶酶体酶天冬氨酰氨基葡糖苷酶（AGA）缺乏引起。除芬兰外，这种疾病在普通人群中较为罕见。由于这种疾病最典型的特征是进行性发育倒退，患者在疾病初期通常没有特定症状，因此早期诊断往往具有挑战性。
我们遇到一名16岁男孩，他在6岁时开始出现言语困难。由于发育出现轻度倒退，他逐渐丧失了日常常见能力。最初通过外显子组测序诊断出他在AGA基因中存在一种新的纯合突变。由于父母近亲结婚，这个结果是合理的。随后证实了AGA酶活性降低。通过基质辅助激光解吸/电离飞行时间质谱（MALDI-TOF-MS）对他的尿液进行回顾性筛查，确定了一种特定的异常代谢物模式。
由于外显子组测序和MALDI-TOF-MS筛查都具有适应性和全面性，未来联合使用这些方法将有助于诊断AGU等罕见的先天性代谢缺陷疾病。
