以骨质破坏为主要表现的戈谢病1例报告及文献复习
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摘要
目的:分析骨破坏为主要表现的戈谢病患者的临床特点,为其临床诊治提供参考。方法:总结1例以骨破坏为主要表现的戈谢病病例的临床资料,结合相关文献复习,分析戈谢病患者临床表现、并发症、治疗方案、预后及最新相关研究进展。结果:患者,男性,49岁,因"右大腿间断性疼痛2年"入院。患者有戈谢病家族史,患者父母近亲结婚(表兄妹),7年前确诊。入院后结合患者病史、临床表现、家族史和各项辅助检查结果,诊断为戈谢病、右股骨骨质破坏和脾功能亢进。患者右侧全股骨呈毁损性破坏,大腿疼痛剧烈,患者无法承担长期酶替代治疗费用,拟行病损切除术。由于患者伴有脾功能亢进、血小板减少等手术禁忌证,先后2次行脾动脉部分栓塞治疗(第1次栓塞体积为25%,第2次栓塞体积为35%)。脾栓塞术后1周复查血常规,脾功能亢进明显改善,血小板计数87×109 L-1、血红蛋白91g·L-1,拟行手术治疗。但是患肢疼痛症状缓解,患者放弃手术治疗。出院建议避免外伤、减少负重,预防病理性骨折,定期随访。结论:近亲结婚致戈谢病。结合患者家族史、临床表现、各项辅助检查可初步诊断,根据葡萄糖脑苷脂酶活性检测可确诊。Ⅰ型戈谢病患者可行酶替代治疗,未行酶替代治疗、病史长者可表现为严重骨质破坏、脾功能亢进,需行手术等对症治疗。
Objective:To analyze the clinical characteristics of a patient with of Gaucher's disease with bone destruction as the main performance,and to provide the reference for its clinical diagnosis and treatment.Methods:The clinical data of a case of Gaucher's disease with bone destruction as the main performance was summarized.Combined with the related literature review,the clinical performance,complications,treatment plan,prognosis and the latest relevant research progress of the patients with Gaucher's disease were analyzed.Results:A male patient,49 years old,was admitted to the hospital due to intermittent right thigh pain for two years,with family history of Gaucher's disease and his parents were consanguineous marriage.The patient was diagnosed as Gaucher's disease 7 years ago.Combined with the patient's history,clinical performance,family history and various auxiliary examination results,the patient was diagnosed as Gaucher's disease,right femur bone destruction,hypersplenism.The patient's right femur was extensively damaged,and the right thigh was severely painful.The patient could not afford the long-term enzyme replacement treatment and planned to have a lesion resection.Because hypersplenism and thrombocytopenia were contraindication for surgery,partial embolization of the splenic artery was performed twice(the first embolization volume was 25%,and the second embolization volume was 35%).Blood cell count was performed one week after spleen embolization,which was significantly improved:platelet count 87×109 L-1,hemoglobin 91 g·L-1,and surgical treatment was planned.However,the pain was relieved and the patient gave up surgery.The patient was recommended to avoid injury,reduce weight-bearing,and prevent the pathological fractures;the patient was followed up regularly.Conclusion:The incidence of Gaucher's disease is increased in consanguineous marriage.A preliminary diagnosis was made based on the family history,clinical performance,and various auxiliary examinations,and further confirmed according to the detection of glucocerebrosidase activity.The patients with type Ⅰ Gaucher's disease are eligible for enzyme replacement therapy.Without enzyme replacement therapy,the patients with chronic history will be concurrent bone destruction,hypersplenism,need symptomatic treatment such as surgery.
Objective:To analyze the clinical characteristics of a patient with of Gaucher's disease with bone destruction as the main performance,and to provide the reference for its clinical diagnosis and treatment.Methods:The clinical data of a case of Gaucher's disease with bone destruction as the main performance was summarized.Combined with the related literature review,the clinical performance,complications,treatment plan,prognosis and the latest relevant research progress of the patients with Gaucher's disease were analyzed.Results:A male patient,49 years old,was admitted to the hospital due to intermittent right thigh pain for two years,with family history of Gaucher's disease and his parents were consanguineous marriage.The patient was diagnosed as Gaucher's disease 7 years ago.Combined with the patient's history,clinical performance,family history and various auxiliary examination results,the patient was diagnosed as Gaucher's disease,right femur bone destruction,hypersplenism.The patient's right femur was extensively damaged,and the right thigh was severely painful.The patient could not afford the long-term enzyme replacement treatment and planned to have a lesion resection.Because hypersplenism and thrombocytopenia were contraindication for surgery,partial embolization of the splenic artery was performed twice(the first embolization volume was 25%,and the second embolization volume was 35%).Blood cell count was performed one week after spleen embolization,which was significantly improved:platelet count 87×109 L-1,hemoglobin 91 g·L-1,and surgical treatment was planned.However,the pain was relieved and the patient gave up surgery.The patient was recommended to avoid injury,reduce weight-bearing,and prevent the pathological fractures;the patient was followed up regularly.Conclusion:The incidence of Gaucher's disease is increased in consanguineous marriage.A preliminary diagnosis was made based on the family history,clinical performance,and various auxiliary examinations,and further confirmed according to the detection of glucocerebrosidase activity.The patients with type Ⅰ Gaucher's disease are eligible for enzyme replacement therapy.Without enzyme replacement therapy,the patients with chronic history will be concurrent bone destruction,hypersplenism,need symptomatic treatment such as surgery.
引文
[1]SOBREIRA E,PIRES R F,CIZMARIK M,et al.Phenotypic and genotypic heterogeneity in Gaucher disease type 1:a comparison between Brazil and the rest-of-the world[J].Mol Genet Metab,2007,90(1):81-86.
[2]BRADY R O,KANFER J N,SHAPIRO D.Metabolism of glucocerebrosidesⅡ.Evidence of an enzymatic deficiency in Gaucher’s disease[J].Biochem Biophys Res Commun,1965,18:221-225.
[3]刘林玉,杜司晨,张进,等.戈谢病致病机制及治疗方法[J].遗传,2015,37(6):510-516.
[4]中华医学会儿科学分会遗传代谢内分泌学组,中华医学会儿科学分会血液学组,中华医学会血液学分会红细胞疾病(贫血)学组.中国戈谢病诊治专家共识(2015)[J].中华儿科杂志,2015,53(4):256-261.
[5]段彦龙,张永红,臧晏,等.酶替代治疗戈谢病72例[J].中华儿科杂志,2006,44(9):653-656.
[6]GRABOWSKI G A.Phenotype,diagnosis,and treatment of Gaucher’s disease[J].Lancet,2008,372(9645):1263-1271.
[7]WENSTRUP R J,ROCA-ESPIAU M,WEINREB N J,et al.Skeletal aspects of Gaucher disease:a review[J].Br JRadiol,2002,75(Suppl 1):A2-A12.
[8]CHAN A,HOLLERAN W M,FERGUSON T,et al.Skin ultrastructural findings in type 2Gaucher disease:diagnostic implications[J].Mol Genet Metab,2011,104(4):631-636.
[9]ELSTEIN D,ABRAHAMOV A,ALTARESCU G,et al.Evolving features in type 3 Gaucher disease on long-term enzyme replacement therapy[J].Blood Cells Mol Dis,2013,50(2):140.
[10]KHALIFA A S,TANTAWY A A,SHAWKY R M,et al.Outcome of enzyme replacement therapy in children with Gaucher disease:The Egyptian experience[J].Egypt J Med Human Genet,2011,12(1):9-14.
[11]李平,袁弥满,蔡则骥,等.大鼠部分脾栓塞后脾脏巨噬细胞吞噬功能的定量测定[J].华中医学杂志,2001,25(6):318-319.
[12]LEE J Y,LEE B H,KIM G H,et al.Clinical and genetic characteristics of Gaucher disease according to phenotypic subgroups[J].Korean J Pediatr,2012,55(2):48-53.
[13]WANG G N,TWIGG G,BUTTERS T D,et al.Synthesis of N-substituted E-hexonolactams as pharmacological chaperones for the treatment of N370S mutant Gaucher disease[J].Org Biomol Chem,2012,10(15):2923-2927.
[14]SINGLA M,ARIVARASAN K,DHIR V,et al.Medical image.an unusual cause of massive splenomegaly in an adult.Gaucher’s disease[J].N Z Med J,2012,125(1361):98-101.
[15]SELDEN N R,UZRI A,HUHN S L,et al.Central nervoussystem stem eell transplantation for children with neuronal ceroid lipofuscinosis[J].J Neurosurg Pediatr,2013,11(6):643-652.
[16]ENQUIST I B,NILSSON E,OOKA A,et al.Effective cell and gene therapy in a murine model of Gaucher disease[J].Proc Natl Acad Sci USA,2006,103(37):13819-13824.
[17]TISCORNIA G,VIVAS E L,MATALONGA L,et al.Neuronopathic Gaucher’s disease:induced pluripotent stem cells for disease modelling and testing chaperone activity of small compounds[J].Hum Mol Genet,2013,22(4):633-645.
[18]MASSARO G,MATTAR C N Z,WONG A M S,et al.Fetal gene therapy for neurodegenerative disease of infants[J].Nat Med,2018.DOI:10.1038/s41591-018-0106-7.
[19]MATTAR C N,ANDREW M S,HOEFER K,et al.Systemic gene delivery following intravenous administration of AAV9to fetal and neonatal mice and late-gestation nonhuman primates[J].FASEB J,2015,29(9):3876-3888.
[2]BRADY R O,KANFER J N,SHAPIRO D.Metabolism of glucocerebrosidesⅡ.Evidence of an enzymatic deficiency in Gaucher’s disease[J].Biochem Biophys Res Commun,1965,18:221-225.
[3]刘林玉,杜司晨,张进,等.戈谢病致病机制及治疗方法[J].遗传,2015,37(6):510-516.
[4]中华医学会儿科学分会遗传代谢内分泌学组,中华医学会儿科学分会血液学组,中华医学会血液学分会红细胞疾病(贫血)学组.中国戈谢病诊治专家共识(2015)[J].中华儿科杂志,2015,53(4):256-261.
[5]段彦龙,张永红,臧晏,等.酶替代治疗戈谢病72例[J].中华儿科杂志,2006,44(9):653-656.
[6]GRABOWSKI G A.Phenotype,diagnosis,and treatment of Gaucher’s disease[J].Lancet,2008,372(9645):1263-1271.
[7]WENSTRUP R J,ROCA-ESPIAU M,WEINREB N J,et al.Skeletal aspects of Gaucher disease:a review[J].Br JRadiol,2002,75(Suppl 1):A2-A12.
[8]CHAN A,HOLLERAN W M,FERGUSON T,et al.Skin ultrastructural findings in type 2Gaucher disease:diagnostic implications[J].Mol Genet Metab,2011,104(4):631-636.
[9]ELSTEIN D,ABRAHAMOV A,ALTARESCU G,et al.Evolving features in type 3 Gaucher disease on long-term enzyme replacement therapy[J].Blood Cells Mol Dis,2013,50(2):140.
[10]KHALIFA A S,TANTAWY A A,SHAWKY R M,et al.Outcome of enzyme replacement therapy in children with Gaucher disease:The Egyptian experience[J].Egypt J Med Human Genet,2011,12(1):9-14.
[11]李平,袁弥满,蔡则骥,等.大鼠部分脾栓塞后脾脏巨噬细胞吞噬功能的定量测定[J].华中医学杂志,2001,25(6):318-319.
[12]LEE J Y,LEE B H,KIM G H,et al.Clinical and genetic characteristics of Gaucher disease according to phenotypic subgroups[J].Korean J Pediatr,2012,55(2):48-53.
[13]WANG G N,TWIGG G,BUTTERS T D,et al.Synthesis of N-substituted E-hexonolactams as pharmacological chaperones for the treatment of N370S mutant Gaucher disease[J].Org Biomol Chem,2012,10(15):2923-2927.
[14]SINGLA M,ARIVARASAN K,DHIR V,et al.Medical image.an unusual cause of massive splenomegaly in an adult.Gaucher’s disease[J].N Z Med J,2012,125(1361):98-101.
[15]SELDEN N R,UZRI A,HUHN S L,et al.Central nervoussystem stem eell transplantation for children with neuronal ceroid lipofuscinosis[J].J Neurosurg Pediatr,2013,11(6):643-652.
[16]ENQUIST I B,NILSSON E,OOKA A,et al.Effective cell and gene therapy in a murine model of Gaucher disease[J].Proc Natl Acad Sci USA,2006,103(37):13819-13824.
[17]TISCORNIA G,VIVAS E L,MATALONGA L,et al.Neuronopathic Gaucher’s disease:induced pluripotent stem cells for disease modelling and testing chaperone activity of small compounds[J].Hum Mol Genet,2013,22(4):633-645.
[18]MASSARO G,MATTAR C N Z,WONG A M S,et al.Fetal gene therapy for neurodegenerative disease of infants[J].Nat Med,2018.DOI:10.1038/s41591-018-0106-7.
[19]MATTAR C N,ANDREW M S,HOEFER K,et al.Systemic gene delivery following intravenous administration of AAV9to fetal and neonatal mice and late-gestation nonhuman primates[J].FASEB J,2015,29(9):3876-3888.