CAJ | 학술논문

目的探讨天冬氨酰基葡萄糖胺尿症(AGU)的临床特征和基因突变特点.方法回顾性分析一家系2例AGU同胞患儿的病例资料,并复习相关文献,分析本病的临床特点、影像学特征、酶学特征和基因突变特点.结果病例1为先证者,男,1岁8个月,因“发热伴肝、脾肿大9d”入院.患儿营养状态中等,发育正常.血常规示血红蛋白78.0 g/L、红细胞3.18×1012/L、白细胞4.06×109/L、中性粒细胞0.236、淋巴细胞0.631、血小板34×109/L、C反应蛋白17 mg/L.血生化示丙氨酸氨基转移酶67.1 U/L、天冬氨酸氨基转移酶74.1 U/L、血清白蛋白32.8g/L、直接胆红素10.5 μmol/L、乳酸脱氢酶301.7 U/L.骨髓细胞学检查示反应性骨髓细胞形态改变;外周血及骨髓涂片中均可见异型淋巴细胞.头颅MRI显示髓鞘发育不良.外周血白细胞天冬氨酰氨基葡萄糖苷酶(AGA)活性5.7 nmol/(g·min)[正常值＞26.6 nmol/(g·min)].基因分析显示患儿AGA基因第3外显子存在一个杂合变异位点c.392C＞ T(p.S131L),为未报道的新突变,来自父亲,未检测到母源基因突变.先证者经抗感染、营养支持及对症治疗无效,1个月后死亡.例2为先证者的哥哥,4岁时因发热,肝、脾肿大就诊,反复呼吸道感染,智力倒退,行为异常,头颅MRI显示双侧大脑、小脑及脑干广泛对称性白质损害,6岁时死亡.总结相关文献发现国内尚未报道,国外报道221例,总结其临床特点,语言发育障碍是多数患儿被父母注意的首个临床症状.结论 AGU缺乏特异性症状,对于不明原因的语言落后伴智力进行性低下的患儿应考虑AGU的可能,争取酶学及基因诊断.c.392C＞T(p.S131L)为AGA基因的一种新突变.
목적 탐토천동안선기포도당알뇨증(AGU)적림상특정화기인돌변특점.방법 회고성분석일가계2례AGU동포환인적병례자료,병복습상관문헌,분석본병적림상특점、영상학특정、매학특정화기인돌변특점.결과 병례1위선증자,남,1세8개월,인“발열반간、비종대9d”입원.환인영양상태중등,발육정상.혈상규시혈홍단백78.0 g/L、홍세포3.18×1012/L、백세포4.06×109/L、중성립세포0.236、림파세포0.631、혈소판34×109/L、C반응단백17 mg/L.혈생화시병안산안기전이매67.1 U/L、천동안산안기전이매74.1 U/L、혈청백단백32.8g/L、직접담홍소10.5 μmol/L、유산탈경매301.7 U/L.골수세포학검사시반응성골수세포형태개변;외주혈급골수도편중균가견이형림파세포.두로MRI현시수초발육불량.외주혈백세포천동안선안기포도당감매(AGA)활성5.7 nmol/(g·min)[정상치＞26.6 nmol/(g·min)].기인분석현시환인AGA기인제3외현자존재일개잡합변이위점c.392C＞ T(p.S131L),위미보도적신돌변,래자부친,미검측도모원기인돌변.선증자경항감염、영양지지급대증치료무효,1개월후사망.례2위선증자적가가,4세시인발열,간、비종대취진,반복호흡도감염,지력도퇴,행위이상,두로MRI현시쌍측대뇌、소뇌급뇌간엄범대칭성백질손해,6세시사망.총결상관문헌발현국내상미보도,국외보도221례,총결기림상특점,어언발육장애시다수환인피부모주의적수개림상증상.결론 AGU결핍특이성증상,대우불명원인적어언락후반지력진행성저하적환인응고필AGU적가능,쟁취매학급기인진단.c.392C＞T(p.S131L)위AGA기인적일충신돌변.
Objective The authors sought to investigate the clinical features and characteristics of genetic mutation in patients with aspartylglucosaminuria.Method Clinical data of two pediatric siblings in a family were analyzed retrospectively and relative literature was reviewed in order to study the clinical features,imaging and enzymatic characteristics and genetic mutations.Result Case 1,the proband,male,he was hospitalized at 20 months of age because of fever and hepatosplenomegaly for nine days.This child was of moderate nutritional status and normal development.Blood tests showed hemoglobin 78.0 g/L,RBC3.18 × l012/L,WBC4.06 × 109/L,neutrophils 0.236,lymphocytes 0.631,platelets 34 × 109/L,Creactive protein 17 mg/L.Blood biochemistry showed alanine aminotransferase 67.1 U/L,aspartate aminotransferase 74.1 U/L,serum albumin 32.8 g/L,direct bilirubin 10.5 μmol/L,lactate dehydrogenase 301.7 U/L.Bone marrow cytology showed reactive morphological changes in bone marrow cells.Atypical lymphocytes could be seen in both peripheral blood and bone marrow smears.Cranial MRI showed poor myelination.Aspartylglucosaminidase activity in peripheral leucocytes of the proband 5.7 nmol/(g · min) vs.normal control ＞ 26.6 nmol/(g · min).On his AGA gene and that of his parents,a heterozygous mutation site located in exon 3,c.392C ＞ T(p.S131L),was identified as a novel mutation inherited from his father.The mutation from his mother has not been detected.The proband was not responsive to the antiinfectious medication,nutritional intervention and symptomatic treatment.He died one month after diagnosis.His elder brother,Case 2,showed fever,recurrent respiratory tract infection and progressive psychomotor regression with hepatosplenomegaly from the age of four years.Cranial MRI revealed extensive symmetrical leukodystrophy in bilateral cerebra,cerebellum and brainstem.He died at the age of six years.Related literature was summarized,and no Chinese AGU cases had been reported; 221 foreign cases were collected.The clinical and imaging characteristics were summarized.Delay in language development was one of the clinical symptoms that the majority of parents of AGU children first noted.Conclusion Patients with aspartylglucosaminuria lack of specific symptoms.For children with unexplained delayed speech and progressive mental retardation,the possibility of AGU should be considered,and efforts be made for enzymatic and genetic diagnosis,c.392C ＞ T (p.S131L) was identified as a novel mutation of AGA gene.