CAJ | 학술논문

目的总结分析2例多种硫酸酯酶缺乏症患儿的临床表现、硫酸酯酶活性及硫酸酯酶修饰因子1(SUMF1)基因的突变情况.方法 2例患儿中例1男,5岁6个月；例2女,5岁2个月,来自2个不同家系,皆因自幼发育落后,伴智力、运动、语言倒退来院就诊.二者都有面容改变、肌张力增高、腱反射亢进、巴氏征阳性、骨骼畸形及皮肤干燥脱屑等多脏器损害表现,病情进展迅速.骨骼X线提示多发性骨发育不良,尿甲苯胺蓝试验强阳性.采用荧光-人工合成底物法检测患者外周血浆或白细胞、成纤维细胞中硫酸酯酶活性；提取患儿及其父母的基因组DNA,针对SUMF1基因设计特异性引物,应用DNA-PCR方法扩增基因的全部外显子及外显子-内含子交界区,对扩增产物进行直接测序分析.结果 2例患者临床表现符合多种硫酸酯酶缺乏症,酶学检测证实患者外周血白细胞、血浆或培养的皮肤成纤维细胞中至少3种硫酸酯酶活性明显降低；SUMF1测序发现例1的基因型为c.793_794insAGT(p.F265X)/c.1045C ＞T (p.R349W),例2的基因型为c.1046G＞C(p.R349P)/c.451A ＞G (p.K151E).其中c.793_794insAGT、c.1046G＞C和c.451A＞G为未见报道的新突变.结论多种硫酸酯酶缺乏症导致神经、骨骼、皮肤等多脏器损害,患者临床表现复杂,需要通过多种硫酸酯酶活性检测和SUMF1基因突变检测明确诊断.2例多种硫酸酯酶缺乏症患者的3个SUMF1突变为新突变,提示我国患者基因突变谱可能不同于其他国家.
목적 총결분석2례다충류산지매결핍증환인적림상표현、류산지매활성급류산지매수식인자1(SUMF1)기인적돌변정황.방법 2례환인중례1남,5세6개월；례2녀,5세2개월,래자2개불동가계,개인자유발육락후,반지력、운동、어언도퇴래원취진.이자도유면용개변、기장력증고、건반사항진、파씨정양성、골격기형급피부간조탈설등다장기손해표현,병정진전신속.골격X선제시다발성골발육불량,뇨갑분알람시험강양성.채용형광-인공합성저물법검측환자외주혈장혹백세포、성섬유세포중류산지매활성；제취환인급기부모적기인조DNA,침대SUMF1기인설계특이성인물,응용DNA-PCR방법확증기인적전부외현자급외현자-내함자교계구,대확증산물진행직접측서분석.결과 2례환자림상표현부합다충류산지매결핍증,매학검측증실환자외주혈백세포、혈장혹배양적피부성섬유세포중지소3충류산지매활성명현강저；SUMF1측서발현례1적기인형위c.793_794insAGT(p.F265X)/c.1045C ＞T (p.R349W),례2적기인형위c.1046G＞C(p.R349P)/c.451A ＞G (p.K151E).기중c.793_794insAGT、c.1046G＞C화c.451A＞G위미견보도적신돌변.결론 다충류산지매결핍증도치신경、골격、피부등다장기손해,환자림상표현복잡,수요통과다충류산지매활성검측화SUMF1기인돌변검측명학진단.2례다충류산지매결핍증환자적3개SUMF1돌변위신돌변,제시아국환자기인돌변보가능불동우기타국가.
Objective Multiple sulfatase deficiency is a rare autosomal recessively inherited lysosomal storage disorder characterized by the accumulation of sulfated lipids and acid mucopolysaccharides.The aim of this study was to explore the clinical manifestations,enzyme activities and SUMF1 gene mutations in two Chinese patients with multiple sulfatase deficiency.Method One boy and one girl from two families were studied.Both patients presented with mental retardation,mild coarse facial features,a neurodegenerative course of disease with loss of sensory and motor function after 2 years of age,ichthyosis and skeletal abnormalities (kyphosis or/and scoliosis).Clinical characteristics indicate multiple sulfatase deficiency.Sulfatases activities in blood leucocytes,plasma or cultured fibroblast of the patients were measured.Genomic DNAs were extracted from peripheral blood leukocytes from the patients and their parents.All SUMF1 gene exons and intron-exon boundaries were amplified by PCR and subjected for direct sequencing.Result In case 1,five sulfatases activities of blood leucocytes and four sulfatases of cultured skin-fibroblasts were analyzed.In case 2,three sulfatases activities of blood leucocytes were tested.Significantly decreased sulfatases activities confirmed the diagnosis of multiple sulfatase deficiency.On SUMF1 gene,c.793_794 insATG (p.P265X)/ c.1045C ＞ T (p.R349W) in case 1 and c.451A ＞ G (p.K151 E) / c.1046G ＞ C (p.R349 Q) in case 2 were detected,respectively.Three novel mutations c.793_ 794insAGT,c.1046G ＞ C and c.451A ＞ G were identified.Conclusions Multiple sulfatase deficiency usually results in multi-organ damage,especially neurologic,skeletal and skin.Sulfatases assay and SUMF1 gene analysis are necessary for the diagnosis.Two Chinese cases with multiple sulfatase deficiency were firstly reported.Three novel mutations were found.It should be considered that the mutation profile of SUMF1 gene in Chinese patients is different from other populations.