Cobos Paulina Nieves, Steglich Cordula, Santer René, Lukacs Zoltan, Gal Andreas
Metabolic Laboratory, Department of Paediatrics, Institute of Clinical Chemistry, Hamburg University Medical Centre, Martinistr. 52, 20246, Hamburg, Germany.
JIMD Rep. 2015;15:123-32. doi: 10.1007/8904_2014_308. Epub 2014 May 6.
As patients with different types of mucopolysaccharidosis (MPS) and mucolipidosis (ML) may present with overlapping clinical features - including coarse face, hepatosplenomegaly, bone dysplasia and claw-hand deformities, collectively also called 'MPS-like phenotype', enzymatic and/or molecular genetic analyses are indispensable for accurate diagnosis and applying specific therapy. In this prospective study, we screened patients with symptoms compatible with MPS for MPS I, II (males) and VI.
Dried blood spots/specimens (DBS) were collected from 200 patients with an MPS-like phenotype and analysed for activities of α-iduronidase (IDUA), iduronate-2-sulphatase (IDS), and arylsulphatase B (ARSB), the enzymes deficient in mucopolysaccharidosis (MPS) type I, II and VI, respectively. For the samples with pathologic enzyme activity, mutational analysis was carried out using the same DBS.
Based on enzymatic analysis of 200 DBS samples, a total of 45 (22.5%) showed low activity; 17 for MPS I (8.5%), 11 for MPS II (5.5%) and 9 for MPS VI (4.5%). Enzyme activities were suggestive for ML II/III in 8 (4.0%) cases. For 41 (91.1%) samples, DNA could be extracted from the filter paper. Mutations were identified in 11 (64.7%), 11 (100%), 9 (100%) and 5 (62.5%) patients putatively diagnosed biochemically with MPS I, II, VI, and ML II/III, respectively.
DBS enzymatic analysis can be used to diagnose MPS/ML. Initial results should be confirmed by a second enzyme assay and/or by molecular genetic testing. Given the advantages of DBS over other sample types in terms of ease of collection, storage and transportation, DBS are particularly useful for screening patients with an MPS-like phenotype in regions lacking specialised laboratories. In order to ascertain the diagnosis in a large number of cases, patients should be assessed in parallel for at least MPS I, II and VI.
不同类型的黏多糖贮积症（MPS）和黏脂贮积症（ML）患者可能表现出重叠的临床特征，包括面容粗糙、肝脾肿大、骨骼发育异常和爪形手畸形，这些特征统称为“MPS样表型”。酶学和/或分子遗传学分析对于准确诊断和应用特定治疗至关重要。在这项前瞻性研究中，我们对具有与MPS相符症状的患者进行了MPS I、II（男性）和VI的筛查。
从200例具有MPS样表型的患者中收集干血斑/标本（DBS），并分析α-L-艾杜糖醛酸酶（IDUA）、艾杜糖醛酸-2-硫酸酯酶（IDS）和芳基硫酸酯酶B（ARSB）的活性，这三种酶分别是黏多糖贮积症（MPS）I型、II型和VI型所缺乏的。对于酶活性异常的样本，使用相同的DBS进行突变分析。
基于对200份DBS样本的酶学分析，共有45份（22.5%）显示活性降低；MPS I型17份（8.5%），MPS II型11份（5.5%），MPS VI型9份（4.5%）。8份（4.0%）样本的酶活性提示为ML II/III型。对于41份（91.1%）样本，可以从滤纸上提取DNA。在分别初步生化诊断为MPS I型、II型、VI型和ML II/III型的患者中，分别有11例（64.7%）、11例（100%）、9例（100%）和5例（62.5%）检测到突变。
DBS酶学分析可用于诊断MPS/ML。初步结果应由第二次酶测定和/或分子遗传学检测来确认。鉴于DBS在采集、储存和运输方面比其他样本类型更具优势，DBS对于在缺乏专业实验室的地区筛查具有MPS样表型的患者特别有用。为了在大量病例中确定诊断，应对患者至少同时进行MPS I型、II型和VI型的评估。
