Inborn errors of metabolism are identified in 5%-26% of infants and children with cardiomyopathy. Although fatty acid oxidation disorders, lysosomal and glycogen storage disorders and organic acidurias are well-known ...Inborn errors of metabolism are identified in 5%-26% of infants and children with cardiomyopathy. Although fatty acid oxidation disorders, lysosomal and glycogen storage disorders and organic acidurias are well-known to be associated with cardiomyopathies, emerging reports suggest that mitochondrial dysfunction and congenital disorders of glycosylation may also account for a proportion of cardiomyopathies. This review article clarifies when primary care physicians and cardiologists should suspect inborn errors of metabolism in a patient with cardiomyopathy, and refer the patient to a metabolic specialist for a further metabolic work up, with specific discussions of "red flags" which should prompt additional evaluation.展开更多
Inborn errors of metabolism (IEM) include a broad spectrum of defects of various gene products that affect interme-diary metabolism in the body. Studying the molecular and biochemical mechanisms of those inherited dis...Inborn errors of metabolism (IEM) include a broad spectrum of defects of various gene products that affect interme-diary metabolism in the body. Studying the molecular and biochemical mechanisms of those inherited disorder, systematically summarizing the disease phenotype and natural history, providing diagnostic rationale and methodology and treatment strategy comprise the context of human biochemical genetics. This session focused on: (1) manifestations of representative metabolic disorders; (2) the emergent technology and application of newborn screening of metabolic disorders using tandem mass spec-trometry; (3) principles of managing IEM; (4) the concept of carrier testing aiming prevention. Early detection of patients with IEM allows early intervention and more options for treatment.展开更多
BACKGROUND Type B lactic acidosis and hypoglycemia can occur in various pediatric conditions.In young children with a history of fasting preceding these metabolic derangements,inborn errors of metabolism should be pri...BACKGROUND Type B lactic acidosis and hypoglycemia can occur in various pediatric conditions.In young children with a history of fasting preceding these metabolic derangements,inborn errors of metabolism should be primarily considered.However,the Warburg effect,a rare metabolic complication,can also manifest in children with hematologic malignancies.Only a few reports of this condition in children have been published in the literature.AIM To identify the clinical course,treatment strategies,and outcomes of childhood hematologic malignancies with type B lactic acidosis.METHODS We performed a comprehensive search of the PubMed,Scopus,and Cochrane databases without any time restriction but limited to English language articles.The databases were last accessed on July 1st,2023.RESULTS A total of 20 publications were included in the analysis,all of which were case reports or case series.No higher quality evidence was available.Among children with hematologic malignancies and Warburg effect,there were 14 cases of acute lymphoblastic leukemia and 6 cases of non-Hodgkin’s lymphoma including our illustrative case.Lactic acidosis occurred in 55%of newly diagnosed cases and 45%of relapsed cases.The mean age was 10.3±4.5 years,and 80%of cases were male.The mean serum lactate was 16.9±12.6 mmol/L,and 43.8%of the cases had concomitant hypoglycemia.Lactic acidosis initially subsided in 80%of patients receiving chemotherapy compared to 60%in the contrast group.The mortality rate of newly diagnosed cases was 45.5%,while the relapsed cases represented a 100%mortality rate.All 8 patients reported before 2001 died from disease-related complications.However,patients described in reports published between 2003 and 2023 had a 54.5%rate of complete remission.CONCLUSION This complication has historically led to fatal outcome;however,patients who received chemotherapy showed a more favorable response.Therefore,it is crucial to promptly initiate specific treatment in this context.展开更多
Inborn errors of metabolism（IEMs） are a large group of inherited disorders characterized by disruption of metabolic pathways due to deficient enzymes, cofactors, or transporters. The rapid advances in the understand...Inborn errors of metabolism（IEMs） are a large group of inherited disorders characterized by disruption of metabolic pathways due to deficient enzymes, cofactors, or transporters. The rapid advances in the understanding of the molecular pathophysiology of many IEMs, have led to significant progress in the development of many new treatments. The institution and continued expansion of newborn screening provide the opportunity for early treatment, leading to reduced morbidity and mortality. This review provides an overview of the diverse therapeutic approaches and recent advances in the treatment of IEMs that focus on the basic principles of reducing substrate accumulation, replacing or enhancing absent or reduced enzyme or cofactor, and supplementing product deficiency. In addition, the challenges and obstacles of current treatment modalities and future treatment perspectives are reviewed and discussed.展开更多
BACKGROUND Inborn error of bile acid synthesis type 4 is a peroxisomal disease with impaired bile acid synthesis caused by a-methylacyl-CoA racemase(AMACR)gene mutation.The disease is usually found in children with mi...BACKGROUND Inborn error of bile acid synthesis type 4 is a peroxisomal disease with impaired bile acid synthesis caused by a-methylacyl-CoA racemase(AMACR)gene mutation.The disease is usually found in children with mild to severe liver disease,cholestasis and poor fat-soluble vitamin absorption.At present,there is no report of inborn errors of bile acid synthesis type 4 in adults with liver disease and poor fat-soluble vitamin absorption.CASE SUMMARY A 71-year-old man was hospitalized in our department for recurrent liver dysfunction.The clinical manifestations were chronic liver disease and yellow skin and sclera.Serum transaminase,bilirubin and bile acid were abnormally increased;and fat-soluble vitamins decreased.Liver cirrhosis and ascites were diagnosed by computed tomography.The patient had poor coagulation function and ascites and did not undergo liver puncture.Genetic testing showed AMACR gene missense mutation.The patient was diagnosed with inborn error of bile acid synthesis type 4.He was treated with ursodeoxycholic acid,liver protection and vitamin supplementation,and jaundice of the skin and sclera was reduced.The indicators of liver function and the quality of life were significantly improved.CONCLUSION When adults have recurrent liver function abnormalities,physicians should be alert to genetic diseases and provide timely treatment.展开更多
目的:分析新生儿重症监护室(neonatal intensive care unit,NICU)中遗传代谢病(或称先天性代谢缺陷,inborn errors of metabolism,IEM)高危新生儿的病因谱及发病特征。方法:联合应用液相色谱-串联质谱(liquid chromatography-tandem mas...目的:分析新生儿重症监护室(neonatal intensive care unit,NICU)中遗传代谢病(或称先天性代谢缺陷,inborn errors of metabolism,IEM)高危新生儿的病因谱及发病特征。方法:联合应用液相色谱-串联质谱(liquid chromatography-tandem mass spectrometry,LC-MS/MS)和气相色谱-质谱(gas chromatography-mass spectrometry,GC-MS)技术,对2007年9月—2012年8月复旦大学附属儿科医院收治的859例IEM高危新生儿进行血尿代谢标志物的检测和分析,并对确诊为IEM患儿的病因和临床表现进行分析。结果:859例IEM高危新生儿中共诊断IEM22例(2.7%),其中氨基酸代谢病11例(50%),以枫糖尿病(7例)多见;有机酸代谢病11例(50%),以甲基丙二酸血症(8例)多见。22例IEM患儿的临床表现各不相同,多在出生后一个短暂的"正常"期后起病,以拒食、呕吐、惊厥发作等消化系统或神经系统症状为主。结论:高危新生儿IEM病因谱复杂多样,以甲基丙二酸血症和枫糖尿病最多见,临床应重视早期联合运用LC-MS/MS和GC-MS技术对NICU中IEM高危新生儿进行IEM检测,以便早期诊断和干预。展开更多
目的:评估南京医科大学附属妇产医院(我院)新生儿重症监护病房(neonatal intensive care unit,NICU)罕见病的发生情况,分析罕见病的变化趋势。方法:选取2013年1月—2020年12月我院分娩出生并在NICU治疗的危重新生儿,血、尿串联质谱筛查...目的:评估南京医科大学附属妇产医院(我院)新生儿重症监护病房(neonatal intensive care unit,NICU)罕见病的发生情况,分析罕见病的变化趋势。方法:选取2013年1月—2020年12月我院分娩出生并在NICU治疗的危重新生儿,血、尿串联质谱筛查及基因检测明确为罕见病,用描述性研究方法对确诊患儿的疾病检出率、临床特征、基因改变及预后随访等情况进行归纳总结。结果:新生儿总量183820例,年分娩量从18863例逐年上升至26511例,年NICU住院患儿从2312例上升至2871例。共筛查出罕见病患儿34例,年罕见病检出率从0.43‰上升至4.39‰。筛查出的罕见病包括神经肌肉-骨骼疾病4例,遗传代谢性疾病18例,内分泌疾病2例,染色体缺失、异常6例,免疫系统疾病1例,其他3例。其中遗传代谢性疾病比例最高(占比约53%),其次为神经肌肉-骨骼疾病(占比约11%)。常规串联质谱筛查诊断的罕见病共15例,其余19例均是通过外显子测序技术确诊。各种罕见病具有其特异的临床表现。34例罕见病患儿中,死亡8例,18例患儿生长发育基本正常,7例患儿存在不同程度生长智力发育落后,1例失访。结论:新生儿罕见病检出率逐年上升,以常染色体遗传代谢性疾病为主,其病死及后期发育落后比例高。加强对新生儿罕见病临床认知,扩大遗传代谢病筛查范围,加强产前咨询和遗传咨询等是实现优生优育、杜绝罕见病危害的关键。展开更多
文摘Inborn errors of metabolism are identified in 5%-26% of infants and children with cardiomyopathy. Although fatty acid oxidation disorders, lysosomal and glycogen storage disorders and organic acidurias are well-known to be associated with cardiomyopathies, emerging reports suggest that mitochondrial dysfunction and congenital disorders of glycosylation may also account for a proportion of cardiomyopathies. This review article clarifies when primary care physicians and cardiologists should suspect inborn errors of metabolism in a patient with cardiomyopathy, and refer the patient to a metabolic specialist for a further metabolic work up, with specific discussions of "red flags" which should prompt additional evaluation.
文摘Inborn errors of metabolism (IEM) include a broad spectrum of defects of various gene products that affect interme-diary metabolism in the body. Studying the molecular and biochemical mechanisms of those inherited disorder, systematically summarizing the disease phenotype and natural history, providing diagnostic rationale and methodology and treatment strategy comprise the context of human biochemical genetics. This session focused on: (1) manifestations of representative metabolic disorders; (2) the emergent technology and application of newborn screening of metabolic disorders using tandem mass spec-trometry; (3) principles of managing IEM; (4) the concept of carrier testing aiming prevention. Early detection of patients with IEM allows early intervention and more options for treatment.
文摘BACKGROUND Type B lactic acidosis and hypoglycemia can occur in various pediatric conditions.In young children with a history of fasting preceding these metabolic derangements,inborn errors of metabolism should be primarily considered.However,the Warburg effect,a rare metabolic complication,can also manifest in children with hematologic malignancies.Only a few reports of this condition in children have been published in the literature.AIM To identify the clinical course,treatment strategies,and outcomes of childhood hematologic malignancies with type B lactic acidosis.METHODS We performed a comprehensive search of the PubMed,Scopus,and Cochrane databases without any time restriction but limited to English language articles.The databases were last accessed on July 1st,2023.RESULTS A total of 20 publications were included in the analysis,all of which were case reports or case series.No higher quality evidence was available.Among children with hematologic malignancies and Warburg effect,there were 14 cases of acute lymphoblastic leukemia and 6 cases of non-Hodgkin’s lymphoma including our illustrative case.Lactic acidosis occurred in 55%of newly diagnosed cases and 45%of relapsed cases.The mean age was 10.3±4.5 years,and 80%of cases were male.The mean serum lactate was 16.9±12.6 mmol/L,and 43.8%of the cases had concomitant hypoglycemia.Lactic acidosis initially subsided in 80%of patients receiving chemotherapy compared to 60%in the contrast group.The mortality rate of newly diagnosed cases was 45.5%,while the relapsed cases represented a 100%mortality rate.All 8 patients reported before 2001 died from disease-related complications.However,patients described in reports published between 2003 and 2023 had a 54.5%rate of complete remission.CONCLUSION This complication has historically led to fatal outcome;however,patients who received chemotherapy showed a more favorable response.Therefore,it is crucial to promptly initiate specific treatment in this context.
文摘Inborn errors of metabolism（IEMs） are a large group of inherited disorders characterized by disruption of metabolic pathways due to deficient enzymes, cofactors, or transporters. The rapid advances in the understanding of the molecular pathophysiology of many IEMs, have led to significant progress in the development of many new treatments. The institution and continued expansion of newborn screening provide the opportunity for early treatment, leading to reduced morbidity and mortality. This review provides an overview of the diverse therapeutic approaches and recent advances in the treatment of IEMs that focus on the basic principles of reducing substrate accumulation, replacing or enhancing absent or reduced enzyme or cofactor, and supplementing product deficiency. In addition, the challenges and obstacles of current treatment modalities and future treatment perspectives are reviewed and discussed.
文摘BACKGROUND Inborn error of bile acid synthesis type 4 is a peroxisomal disease with impaired bile acid synthesis caused by a-methylacyl-CoA racemase(AMACR)gene mutation.The disease is usually found in children with mild to severe liver disease,cholestasis and poor fat-soluble vitamin absorption.At present,there is no report of inborn errors of bile acid synthesis type 4 in adults with liver disease and poor fat-soluble vitamin absorption.CASE SUMMARY A 71-year-old man was hospitalized in our department for recurrent liver dysfunction.The clinical manifestations were chronic liver disease and yellow skin and sclera.Serum transaminase,bilirubin and bile acid were abnormally increased;and fat-soluble vitamins decreased.Liver cirrhosis and ascites were diagnosed by computed tomography.The patient had poor coagulation function and ascites and did not undergo liver puncture.Genetic testing showed AMACR gene missense mutation.The patient was diagnosed with inborn error of bile acid synthesis type 4.He was treated with ursodeoxycholic acid,liver protection and vitamin supplementation,and jaundice of the skin and sclera was reduced.The indicators of liver function and the quality of life were significantly improved.CONCLUSION When adults have recurrent liver function abnormalities,physicians should be alert to genetic diseases and provide timely treatment.
基金supported by Shanghai Rising-Star Program (No.09QA1404700)Shanghai Health Bureau (No.2007145)+1 种基金Chinese Hi-Tech Research and Development Program (No.2007AA02Z447)Shanghai Government Foundations (No.2008ZD001)
文摘目的:分析新生儿重症监护室(neonatal intensive care unit,NICU)中遗传代谢病(或称先天性代谢缺陷,inborn errors of metabolism,IEM)高危新生儿的病因谱及发病特征。方法:联合应用液相色谱-串联质谱(liquid chromatography-tandem mass spectrometry,LC-MS/MS)和气相色谱-质谱(gas chromatography-mass spectrometry,GC-MS)技术,对2007年9月—2012年8月复旦大学附属儿科医院收治的859例IEM高危新生儿进行血尿代谢标志物的检测和分析,并对确诊为IEM患儿的病因和临床表现进行分析。结果:859例IEM高危新生儿中共诊断IEM22例(2.7%),其中氨基酸代谢病11例(50%),以枫糖尿病(7例)多见;有机酸代谢病11例(50%),以甲基丙二酸血症(8例)多见。22例IEM患儿的临床表现各不相同,多在出生后一个短暂的"正常"期后起病,以拒食、呕吐、惊厥发作等消化系统或神经系统症状为主。结论:高危新生儿IEM病因谱复杂多样,以甲基丙二酸血症和枫糖尿病最多见,临床应重视早期联合运用LC-MS/MS和GC-MS技术对NICU中IEM高危新生儿进行IEM检测,以便早期诊断和干预。
文摘目的:评估南京医科大学附属妇产医院(我院)新生儿重症监护病房(neonatal intensive care unit,NICU)罕见病的发生情况,分析罕见病的变化趋势。方法:选取2013年1月—2020年12月我院分娩出生并在NICU治疗的危重新生儿,血、尿串联质谱筛查及基因检测明确为罕见病,用描述性研究方法对确诊患儿的疾病检出率、临床特征、基因改变及预后随访等情况进行归纳总结。结果:新生儿总量183820例,年分娩量从18863例逐年上升至26511例,年NICU住院患儿从2312例上升至2871例。共筛查出罕见病患儿34例,年罕见病检出率从0.43‰上升至4.39‰。筛查出的罕见病包括神经肌肉-骨骼疾病4例,遗传代谢性疾病18例,内分泌疾病2例,染色体缺失、异常6例,免疫系统疾病1例,其他3例。其中遗传代谢性疾病比例最高(占比约53%),其次为神经肌肉-骨骼疾病(占比约11%)。常规串联质谱筛查诊断的罕见病共15例,其余19例均是通过外显子测序技术确诊。各种罕见病具有其特异的临床表现。34例罕见病患儿中,死亡8例,18例患儿生长发育基本正常,7例患儿存在不同程度生长智力发育落后,1例失访。结论:新生儿罕见病检出率逐年上升,以常染色体遗传代谢性疾病为主,其病死及后期发育落后比例高。加强对新生儿罕见病临床认知,扩大遗传代谢病筛查范围,加强产前咨询和遗传咨询等是实现优生优育、杜绝罕见病危害的关键。
