Suppr超能文献

极低的芳基硫酸酯酶A酶活性不一定会引发症状:一项长期随访及文献综述

Extremely low arylsulfatase A enzyme activity does not necessarily cause symptoms: A long-term follow-up and review of the literature.

作者信息

Laugwitz Lucia, Santhanakumaran Vidiyaah, Spieker Mareike, Boehringer Judith, Bender Benjamin, Gieselmann Volkmar, Beck-Woedl Stefanie, Bruchelt Gernot, Harzer Klaus, Kraegeloh-Mann Ingeborg, Groeschel Samuel

机构信息

Institute of Medical Genetics and Applied Genomics University of Tübingen Tübingen Germany.

Department of Neuropediatrics, Developmental Neurology and Social Paediatrics University of Tübingen Tübingen Germany.

出版信息

JIMD Rep. 2022 May 4;63(4):292-302. doi: 10.1002/jmd2.12293. eCollection 2022 Jul.

Abstract

Metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal storage disease caused by deficiency of arylsulfatase A (ARSA). Heterozygous carriers of disease-causing variants and individuals harbouring pseudodeficiency alleles in the gene exhibit reduced ARSA activity. In the context of these genotypes, low ARSA activity has been suggested to lead to an atypical form of MLD or other neurological abnormalities, but data are limited. The aim of our study was to analyse the impact of low ARSA activity in two subjects who are heterozygous for the ARSA pseudodeficiency allele and a disease-causing variant. Biochemical testing included ARSA activity measurements and urinary sulfatide analysis. Biochemical data of a large cohort of MLD patients, heterozygotes, pseudodeficient individuals and healthy controls were analysed. MRI was performed at 3T using T1- and T2-weighted sequences and MR spectroscopy. We present two long-term follow-ups who are heterozygous for the pseudodeficiency allele and a disease-causing variant in the gene in cis. The two related index cases exhibit markedly reduced ARSA activity compared to controls and heterozygous carriers. The neurological evaluation and MRI do not reveal any abnormalities. Our data underline that extremely low enzyme activity due to a pseudodeficiency allele and a disease-causing variant in the gene even in does not lead to clinical symptoms or pre-symptomatic MRI changes suspicious for MLD. The review of literature corroborates that any association of low ARSA activity with disease features remains questionable. It seems important to combine the measurement of ARSA activity with elevated sulfatide as well as genetic testing, as done in current newborn screening approaches. Heterozygosity for metachromatic leukodystrophy and an arylsulfatase A pseudodeficiency allele does not cause neurological or neuropsychiatric features.

摘要

异染性脑白质营养不良(MLD)是一种常染色体隐性溶酶体贮积病,由芳基硫酸酯酶A(ARSA)缺乏引起。致病变体的杂合携带者以及该基因中携带假缺陷等位基因的个体,其ARSA活性降低。在这些基因型背景下,有人提出低ARSA活性会导致非典型形式的MLD或其他神经异常,但相关数据有限。我们研究的目的是分析两名携带ARSA假缺陷等位基因和致病变体的杂合子个体中低ARSA活性的影响。生化检测包括ARSA活性测量和尿硫脂分析。我们分析了一大组MLD患者、杂合子、假缺陷个体和健康对照的生化数据。使用T1加权和T2加权序列以及磁共振波谱在3T下进行磁共振成像(MRI)。我们展示了两名携带假缺陷等位基因和该基因顺式致病变体的杂合子的长期随访情况。与对照和杂合携带者相比,这两名相关的索引病例显示出明显降低的ARSA活性。神经学评估和MRI未发现任何异常。我们的数据强调,即使在基因中,由于假缺陷等位基因和致病变体导致的极低酶活性也不会导致临床症状或可疑为MLD的症状前MRI变化。文献综述证实,低ARSA活性与疾病特征之间的任何关联仍存在疑问。将ARSA活性测量与升高的硫脂以及基因检测相结合似乎很重要,就像当前新生儿筛查方法中所做的那样。异染性脑白质营养不良和芳基硫酸酯酶A假缺陷等位基因的杂合性不会导致神经或神经精神特征。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a04/9259399/47408c93767b/JMD2-63-292-g001.jpg

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验