黏多糖贮积症47例的常见酶学分型

Enzymatic diagnosis of 47 cases with mucopolysaccharidosis

目的对临床疑似黏多糖贮积症患儿进行常见酶学分型。方法收集70例临床疑似黏多糖贮积症的患儿，临床疑似黏多糖贮积症的指征包括：生长落后，丑陋面容，骨骼畸形，肝脾增大，智力落后，关节僵硬／松弛等。收集疑似黏多糖贮积症患儿外周血，分离白细胞后，用人工荧光底物法和生物化学方法，分别检测导致Ⅰ，Ⅱ，ⅣA，ⅣB，Ⅵ及Ⅶ缺陷的酶，α-L-艾杜糖酶，艾杜糖醛酸硫酸酯酶，半乳糖胺-6-硫酸硫酸酯酶，β-半乳糖苷酶，芳基硫酸酯酶B及β葡萄糖醛酸酶的活性。结果在70例可疑患儿中，共确诊黏多糖贮积症47例，其中I型7例（占确诊黏多糖贮积症例数的15％），Ⅱ型28例（59％），ⅣA型12例（26％），未发现ⅣB，Ⅵ及Ⅶ型的患儿。黏多糖贮积症Ⅱ型患儿临床表型多样，ⅣA型患儿中67％有典型的关节松弛表现。结论Ⅱ型可能是中国人黏多糖贮积症中最主要的一型，其他较常见的是ⅣA型和Ⅰ型。

Objective With the emergence of enzyme replacement therapy and progress in bone marrow transplantation, treatment of mucopolysaccharidosis （MPS） is much more promising than ever. In order to benefit from these therapies, determination of the defective enzyme is the prerequisite for any individual patient. To make definite diagnosis for patients suspected of having MPS clinically, the authors established six lysosomal enzymatic assays for leucocytes, including alpha-L-iduronidase, iduronate-2- sulfatase, N-acetylgalactosamine 6-sulfatase, beta-galactosidase, arylsulfatase B, beta-glucuronidase, which are the corresponding enzymes of type I , type Ⅱ , type Ⅳ A, type Ⅳ B, type Ⅵ, and type Ⅶ, respectively. Method Seventy patients suspected of having MPS were enrolled from outpatient clinics of the Department of Pediatric Endocrinologic, Genetic and Metabolic Diseases in Xinhua Hospital. Their ages spanned from 10 months to 25 years with the average age 5.7 years. Of them 49 were mate and 21 were female. Leukocytes were isolated with Dextran from peripheral blood of suspected patients. Activity of leukocyte alpha-L-iduronidase, iduronate-2-sulfatase, N-acetylgalactosamine 6-sulfatase, beta-galactosidase, beta-glucuronidase were measured using their specific artificial fluorescent substrates, while arylsulfatase B were determined by colorimetric assay with dipotassium 2-hydroxy-5-nitrophenyl sulfate as the substrate. Result Of the 70 clinically suspected cases totally 47 were confirmed of having mucopolusaccharidosis, of whom 7 cases were type I , 28 cases type Ⅱ , 12 cases type ⅣA. These data show that type Ⅱ is the predominant form of MPS in China, succeeded by MPS type ⅣA. It was also noted that type Ⅱ has the most variable clinical manifestations and 8 out of 12 type IV A patients had the unique lax joints. Conclusion The present study suggest that type Ⅱ might be the predominant form of MPS cases in China, followed by type ⅣA and type I.