目的：探讨黏多糖病（MPS）疾病谱及其临床特点。方法：对2009年1月至2011年12月75例高度疑似MPS患儿同时进行尿黏多糖（GAG）定量和电泳分析以及7种MPS酶学分析。采用荧光分析法分别检测白细胞α-L-艾杜糖酶、艾杜糖-2-硫酸酯酶、α-N-乙酰氨基葡糖苷酶、半乳糖胺-6-硫酸酯酶、β-半乳糖苷酶、芳基硫酸酯酶B及β-葡萄糖醛酸酶活性。结果：根据临床、放射学及酶学检查确诊MPS 52例，年龄4.0±2.2岁，其中I型5例（10%），Ⅱ型20例（38%），ⅣA型20例（38%），Ⅵ型6例（12%），Ⅶ型1例（2%），未发现ⅢB、ⅣB型患儿。除2例ⅣA型患儿外，其余50例MPS 患儿尿GAG/Gr比值均较同龄儿增高。尿GAG定量增高者均确诊为MPS。绝大多数患儿于生后1~2岁起病，常伴有疝、心脏瓣膜病。Ⅰ、Ⅱ、Ⅵ 型患儿表现面容丑陋、皮肤粗糙、矮小、关节僵硬及活动受限，ⅣA型主要表现为矮小、骨骼畸形及关节松弛。结论：MPS Ⅱ型和ⅣA型是MPS最常见类型，其次是Ⅵ型及Ⅰ型。MPS患儿以特殊外貌为临床特点，包括面容丑陋、皮肤粗糙、矮小、骨骼畸形等。尿GAG定量测定可作为一种简便、快速、可靠的MPS筛查方法在临床上推广应用。
Abstract
OBJECTIVE: To explore the incidence of various types of mucopolysaccharidosis (MPS) and their clinical characteristics. METHODS: A total of 75 children highly suspected as having MPS underwent quantitative and electrophoretic analysis of urinary glycosaminoglycans (GAGs) and enzymatic analysis of seven types of MPS from January 2009 to December 2011. Fluorescence assay was used to measure the activities of α-L-iduronidase, iduronate-2-sulfatase, α-N-acetylglucosaminidase, galactosamine-6-sulfatase, β-galactosidase, arylsulfatase B and β-glucuronidase in the white blood cells. RESULTS: A total of 52 cases were confirmed with MPS based on clinical, radiological, and enzymatic examinations. The 52 cases, with a mean age of 4.0±2.2 years, included 5 cases of MPS I (10%), 20 cases of MPS II (38%), 20 cases of MPS IVA (38%), 6 cases of MPS VI (12%) and 1 case of MPS VII (2%). No MPS IV B cases or MPS IIIB cases were found. Compared with healthy children of the same age, the GAG/Cr ratio was significantly elevated in 50 confirmed cases of MPS (two MPS IVA cases having no increased ratio). All children with increased urinary GAGs had a confirmed diagnosis of MPS. The age of onset was between 1 and 2 years after birth in most cases, and often complicated by hernia and valvular heart disease. Children with MPS I, MPS II, and MPS VI presented with ugly and unsmooth face, short stature, joint stiffness, and limitation of motion, while children with MPS IVA presented with short stature, skeletal dysplasia, and joint laxity. CONCLUSIONS: Type IVA and type II are the most common in MPS cases, followed by type VI and type I. MPS children are characterized by special appearances including ugly and unsmooth facial appearance, short stature and skeletal dysplasia. Quantitative analysis of urinary GAG, as a simple, rapid, and reliable method, is recommended for screening of MPS.
关键词
黏多糖病 /
酶测定 /
尿黏多糖 /
儿童
Key words
Mucopolysaccharidosis /
Enzymatic assay /
Urinary glycosaminoglycans /
Child
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参考文献
［1］赵小媛，黄永兰，社勇，林文春，周志红，刘丽. 尿黏多糖定量测定及其临床应用［J］.中国儿童保健杂志，2010，18（11）：885-888.
［2］林群娣，光炜，蒋玮莹. 琼脂糖凝胶电泳检测尿黏多糖方法的建立［J］. 广东医学，1999，20（9）：694.
［3］张惠文，王瑜，叶军，邱文娟，韩连书，高晓岚，等. 黏多糖贮积症47例的常见酶学分型［J］. 中华儿科杂志，2009，47（4）：276-280.
［4］Beesley CE, Meaney CA, Greenland G, Adams V, Vellodi A, Young EP, et al. Mutational analysis of 85 mucopelysaccharidosis type I families: frequency of known mutations, identification of 17 novel mutations and in vitro expression of missense mutations［J］. Hum Genet, 2001, 109(5): 503-511.
［5］Voznyi YV, Keulemans JL, van Diggelen OP. A fluorimetric enzyme assay for the diagnosis of MPS II (Hunter disease) ［J］. J Inherit Metab Dis, 2001, 24(6): 675-680.
［6］Kleijer WJ, Geilen GC, Garritsen V, Huijmans JG, Los FJ, Voznyi YV, et al. First-trimester diagnosis of Morquio disease type A［J］. Prenat Diagn, 2000, 20(3): 183-185.
［7］Iwasaki H, Watanabe H, Iida M, Ogawa S, Tabe M, Higaki K, et al. Fibroblast screening for chaperone therapy in beta-galactnsidosis［J］. Brain Dev, 2006, 28(8): 482-486.
［8］Chamoles NA, Blanco MB, Gaggioli D, Casentini C. Hurler-like phenotype: Enzymatic diagnosis in dried blood spots on filter paper［J］. Clin Chem, 2001, 47(12): 2098-2102.
［9］郭玉风，施惠平，张为民，罗会元，韩璐亚，赵时敏．黏多糖贮积症Ⅵ型的病例诊断与产前诊断［J］. 中国优生遗传杂志，1995，3（2）：21-24.
［10］Vervoort R, Gitzelmann R, Bosshard N, Maire I, Liebaers I, Lissens W. Low beta-glucuronidase enzyme activity and mutations in the human beta-glucuronidase gene in mild mucopolysaccharidosis type VII, pseudodeficiency and a heterozygote［J］. Hum Genet, 1998, 102(1):69-78.
［11］Marsh J, Fensom AH. 4-Methylumbelliferyl alpha-N-acetylglucosaminidase activity for diagnosis of Sanfilippo B disease［J］. Clin Genet, 1985, 27(3): 258-262.
［12］Lin HY, Lin SP, Chuang CK, Niu DM, Chen MR, Tsai FJ, et al. Incidence of the mucopolysaccharidoses in Taiwan, 1984-2004［J］. Am J Med Genet A, 2009, 149A(5): 960-964.
［13］Baehner F, Schmiedeskamp C, Krummenauer F, Miebach E, Bajbouj M, Whybra C, et al. Cumulative incidence rates of the mucopolysaccharidoses in Germany［J］. J Inherit Metab Dis, 2005, 28(6): 1011-1017.
［14］Coelho JC, Wajner M, Burin MG, Vargas CR, Giugliani R. Selective screening of 10000 high-risk Brazilian patients for the detection of inborn errors of metabolism［J］. Eur J Pediatr, 1997, 156(8): 650-654.
［15］Nelson J, Crowhurst J, Carey B, Greed L. Incidence of the mucopolysaccharidoses in Western Australia［J］. Am J Med Genet A, 2003, 123A(3): 310-313.
［16］Alonso-Fernández JR, Fidalgo J, Colón C. Neonatal screening for mucopolysaccharidoses by determination of glycosaminoglycans in the eluate of urine-impregnated paper: preliminary results of an improved DMB-based procedure［J］. J Clin Lab Anal, 2010, 24(3): 149-153.
［17］da Silva EM, Strufaldi MW, Andriolo RB, Silva LA. Enzyme replacement therapy with idursulfase for mucopolysaccharidosis type II (Hunter syndrome) ［J］. Cochrane Database Syst Rev, 2011, (11): CD008185.
［18］黄永兰，李社勇，赵小媛，刘鸿圣，区小冰，刘丽. 黏多糖病Ⅶ型一例并文献复习［J］. 中华儿科杂志, 2011, 49(6): 455-458.
［19］Monta-o AM, Tomatsu S, Gottesman GS, Smith M, Orii T. International Morquio A Registry:clinical manifestation and natural course of Morquio A disease［J］. J Inherit Metab Dis, 2007, 30(2): 165-174.
［20］Nelson J, Thomas PS. Clinical findings in 12 patients with MPS IV A (Morquio′s disease). Further evidence for heterogeneity. Part III: Odontoid dysplasia［J］. Clin Genet, 1988, 33(2): 126-130.
［21］Ransford AO, Crockard HA, Stevens JM, Modaghegh S. Occipito-atlanto-axial fusion in Morquio-Brailsford syndrome. A ten-year experience［J］. J Bone Joint Surg Br, 1996, 78(2): 307-313.
［22］John A, Fagondes S, Schwartz I, Azevedo AC, Barrios P, Dalcin P, et al. Sleep abnormalities in untreated patients with mucopolysaccharidosis type VI［J］. Am J Med Genet A, 2011, 155A(7): 1546-1551.
［23］Schwartz IV, Ribeiro MG, Mota JG, Toralles MB, Correia P, Horovitz D, et al. A clinical study of 77 patients with mucopolysaccharidosis type II［J］. Acta Paediatr Suppl, 2007, 96(455):63-70.
［24］Sohn YB, Choi EW, Kim SJ, Park SW, Kim SH, Cho SY, et al. Retrospective analysis of the clinical manifestations and survival of Korean patients with mucopolysaccharidosis type II: Emphasis on the cardiovascular complication and mortality cases［J］. Am J Med Genet A, 2011, doi: 10.1002/ajmg.a.34371［Epub ahead of print］.
［25］Scarpa M, Almássy Z, Beck M, Bodamer O, Bruce IA, De Meirleir L, et al. Mucopolysaccharidosis type II: European recommendations for the diagnosis and multidisciplinary management of a rare disease［J］. Orphanet J Rare Dis, 2011, 6: 72.
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