尿糖胺聚糖水平与黏多糖贮积症表型之间的关系。

The relationships between urinary glycosaminoglycan levels and phenotypes of mucopolysaccharidoses.

作者信息

Lin Hsiang-Yu, Lee Chung-Lin, Lo Yun-Ting, Wang Tuan-Jen, Huang Sung-Fa, Chen Tzu-Lin, Wang Yu-Shan, Niu Dau-Ming, Chuang Chih-Kuang, Lin Shuan-Pei

机构信息

Department of Medicine, Mackay Medical College, New Taipei City, Taiwan.

Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan.

出版信息

Mol Genet Genomic Med. 2018 Nov;6(6):982-992. doi: 10.1002/mgg3.471. Epub 2018 Sep 16.

DOI:10.1002/mgg3.471

PMID:30296009

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6305646/

Abstract

BACKGROUND

The aim of this study was to use the liquid chromatography/tandem mass spectrometry (LC-MS/MS) method to quantitate levels of three urinary glycosaminoglycans (GAGs; dermatan sulfate [DS], heparan sulfate [HS], and keratan sulfate [KS]) to help make a correct diagnosis of mucopolysaccharidosis (MPS).

METHODS

We analyzed the relationships between phenotypes and levels of urinary GAGs of 79 patients with different types of MPS.

RESULTS

The patients with mental retardation (n = 21) had significantly higher levels of HS than those without mental retardation (n = 58; 328.8 vs. 3.2 μg/ml, p < 0.001). The DS levels in the patients with hernia, hepatosplenomegaly, claw hands, coarse face, valvular heart disease, and joint stiffness were higher than those without. Twenty patients received enzyme replacement therapy (ERT) for 1-12.3 years. After ERT, the KS level decreased by 90% in the patients with MPS IVA compared to a 31% decrease in the change of dimethylmethylene blue (DMB) ratio. The DS level decreased by 79% after ERT in the patients with MPS VI compared to a 66% decrease in the change of DMB ratio.

CONCLUSIONS

The measurement of GAG fractionation biomarkers using the LC-MS/MS method is a more sensitive and reliable tool than the DMB ratio for MPS high-risk screening, diagnosis, subclass identification, and monitoring the efficacy of ERT.

摘要

背景

本研究旨在使用液相色谱/串联质谱（LC-MS/MS）方法定量检测三种尿糖胺聚糖（GAGs；硫酸皮肤素[DS]、硫酸乙酰肝素[HS]和硫酸角质素[KS]）的水平，以帮助正确诊断黏多糖贮积症（MPS）。

方法

我们分析了79例不同类型MPS患者的表型与尿GAGs水平之间的关系。

结果

智力发育迟缓患者（n = 21）的HS水平显著高于非智力发育迟缓患者（n = 58；328.8 vs. 3.2 μg/ml，p < 0.001）。有疝气、肝脾肿大、爪形手、面容粗糙、心脏瓣膜病和关节僵硬的患者的DS水平高于无这些症状者。20例患者接受了1至12.3年的酶替代疗法（ERT）。ERT后，MPS IVA患者的KS水平下降了90%，而二甲亚甲基蓝（DMB）比值变化下降了31%。MPS VI患者ERT后DS水平下降了79%，而DMB比值变化下降了66%。