Dvorakova L, Vlaskova H, Sarajlija A, Ramadza D P, Poupetova H, Hruba E, Hlavata A, Bzduch V, Peskova K, Storkanova G, Kecman B, Djordjevic M, Baric I, Fumic K, Barisic I, Reboun M, Kulhanek J, Zeman J, Magner M
Institute of Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.
Department of Metabolism and Clinical Genetics, Mother and Child Health Care Institute of Serbia, Belgrade, Serbia.
Clin Genet. 2017 May;91(5):787-796. doi: 10.1111/cge.12927. Epub 2017 Mar 17.
Mucopolysaccharidosis type II (Hunter syndrome, MPS II, OMIM 309900) is an X-linked lysosomal storage disorder caused by deficiency of iduronate-2-sulfatase (IDS). We analyzed clinical and laboratory data from 44 Slavic patients with this disease. In total, 21 Czech, 7 Slovak, 9 Croatian and 7 Serbian patients (43 M/1 F) were included in the study (median age 11.0 years, range 1.2-43 years). Birth prevalence ranged from 1:69,223 (Serbia) to 1:192,626 (Czech Rep.). In the majority of patients (71%), the disease manifested in infancy. Cognitive functions were normal in 10 patients. Four, six and 24 patients had mild, moderate, and severe developmental delay, respectively, typically subsequent to developmental regression (59%). Residual enzyme activity showed no predictive value, and estimation of glycosaminoglycans (GAGs) had only limited importance for prognosis. Mutation analysis performed in 36 families led to the identification of 12 novel mutations, eight of which were small deletions/insertions. Large deletions/rearrangements and all but one small deletion/insertion led to a severe phenotype. This genotype-phenotype correlation was also identified in six cases with recurrent missense mutations. Based on patient genotype, the severity of the disease may be predicted with high probability in approximately half of MPS II patients.
II型粘多糖贮积症（亨特综合征，MPS II，OMIM 309900）是一种X连锁溶酶体贮积症，由艾杜糖醛酸-2-硫酸酯酶（IDS）缺乏引起。我们分析了44例患有这种疾病的斯拉夫患者的临床和实验室数据。该研究共纳入21例捷克患者、7例斯洛伐克患者、9例克罗地亚患者和7例塞尔维亚患者（43名男性/1名女性）（中位年龄11.0岁，范围1.2 - 43岁）。出生患病率从1:69,223（塞尔维亚）到1:192,626（捷克共和国）不等。在大多数患者（71%）中，疾病在婴儿期表现出来。10例患者的认知功能正常。分别有4例、6例和24例患者有轻度、中度和重度发育迟缓，通常继发于发育倒退（59%）。残余酶活性没有预测价值，糖胺聚糖（GAGs）的评估对预后的重要性也有限。对36个家系进行的突变分析导致鉴定出12个新突变，其中8个是小缺失/插入。大缺失/重排以及除一个小缺失/插入外的所有突变均导致严重表型。在6例复发性错义突变病例中也发现了这种基因型-表型相关性。基于患者基因型，大约一半的MPS II患者可以高概率预测疾病的严重程度。
