摘要目的 通过1例疑诊黏多糖病11年终获确诊的家系,对黏多糖贮积症Ⅶ型进行研究.方法 患儿,女,12岁时来院,主因“发现骨骼畸形11年,疑似黏多糖病”就诊,对临床表现及影像学特点进行分析,取外周血白细胞进行溶酶体酶活性分析和基因分析.母亲第2次妊娠19周时抽取羊水,通过羊水细胞基因分析进行产前诊断.结果 患儿1岁时家长发现其肋缘外翻、鸡胸,疑诊“骨发育不良”.患儿智力正常,易疲劳,11年来进行性骨骼改变,面容粗陋,大头,体格发育落后,12岁时身高为147 cm(-1 SD).X线检查显示双侧锁骨、肋骨略增粗,脊柱略呈S型弯曲,部分椎体变扁,腰椎以L3为中心后突畸形,L3、L4椎体前缘呈“鸟嘴样”改变.超声心动图显示主动脉瓣叶增厚,关闭不良,二尖瓣前叶略厚,瓣尖对合欠佳.外周血白细胞溶酶体酶活性分析显示β-葡糖醛酸苷酶显著降低[0.2 nmol/(g·min)],符合黏多糖贮积症Ⅶ型.GUSB基因分析显示患儿存在c.1832G＞ C(p.R611P)和c.1244 +3G＞C(剪切)2个突变,父母各携带1个杂合突变,均为未报道的新突变.患儿母亲羊水细胞GUSB基因仅存在c.1832G＞C突变,明确胎儿为携带者,未患与先证者相同的疾病.结论 黏多糖贮积症Ⅶ型是一种严重的进行性退行性疾病,诊断困难,预后不良,迄今尚无有效治疗方法.β-葡糖醛酸苷酶活性测定及GUSB基因分析是确诊的关键技术.本例患儿为中间型,GUSB基因存在2个新突变,母亲第2次妊娠中期通过羊水细胞基因分析对胎儿成功进行了产前诊断.

abstractsObjective To study the clinical and laboratory features of mucopolysaccharidosis type Ⅶ through a difficult case with suspected mucopolysaccharidosis for 11 years.Methods The proband,a girl,was hospitalized at the age of 12 with the suspicion of mucopolysaccharidosis because of skeletal dysplasia.The clinical and imaging investigation were analyzed.Peripheral blood leukocytes β-glucuronidase assay and genetic studies were performed.The mother of the patient visited us at second trimester pregnancy seeking for prenatal diagnosis.GUSB gene mutation analysis of amniocytes was performed for prenatal diagnosis.Results Osteodysplasty had been noticed in the patient at the age of 1 owing to presence of costal margin valgus and pigeon breast.The patient had generally normal intelligence with easy fatigue,progressive skeletal changes,coarse facial features and macrocephaly.Her physical growth was retarded.Her body height was 147 cm (-1 SD) at the age of 12 years.X-ray examination revealed bilateral clavicle and ribs slightly thicker,spine slightly S-shaped bending,some vertebrae flat and lumbar L3 center protrusion deformity,L3 and L4 vertebral showed beak-like changes.Ultrasonic cardiogram examination revealed aortic valve leaf thickening with poor closure function and the mitral valve slightly thickened,cusps poor pointed.Significantly deceased β-glucuronidase activity in peripheral leucocytes [0.2 nmol/(g · min)] supported the diagnosis of mucopolysaccharidosis type Ⅶ.In her GUSB gene,2 novel mutations,c.1832G ＞ C (p.R611P) and c.1244 +3G ＞ C (splicing) were identified,and each parent carried 1 mutation.One heterozygous mutation (c.1832G ＞ C) was detected from cultured amniocytes indicating that the fetus was a carrier of mucopolysaccharidosis type Ⅶ like the father.Conclusions Mucopolysaccharidosis type Ⅶ is a severe progressive degenerative disease with poor prognosis and there is not effected treatment.Diagnosis depends upon enzyme assay and gene testing.In this study,a Chinese family affected by mucopolysaccharidosis type Ⅶ middle type was reported.Two novel mutations on GUSB gene were identified.Prenatal diagnosis to the fetus of this family was performed through amniocytes gene analysis.