Glycogen storage diseases （GSD） are inherited metabolic disorders of glycogen metabolism. Different hormones, including insulin, glucagon, and cortisol regulate the relationship of glycolysis, gluconeogenesis and gl...Glycogen storage diseases （GSD） are inherited metabolic disorders of glycogen metabolism. Different hormones, including insulin, glucagon, and cortisol regulate the relationship of glycolysis, gluconeogenesis and glycogen synthesis. The overall GSD incidence is estimated 1 case per 20000-43000 live births. There are over 12 types and they are classified based on the enzyme deficiency and the affected tissue. Disorders of glycogen degradation may affect primarily the liver, the muscle, or both. Type I a involves the liver, kidney and intestine （and I b also leukocytes）, and the clinical manifestations are hepatomegaly, failure to thrive, hypoglycemia, hyperlactatemia, hyperuricemia and hyperlipidemia. Type Ilia involves both the liver and muscle, and lib solely the liver. The liver symptoms generally improve with age. Type IV usually presents in the first year of life, with hepatomegaly and growth retardation. The disease in general is progressive to cirrhosis. Type Ⅵ and Ⅳ are a heterogeneous group of diseases caused by a deficiency of the liver phosphorylase and phosphorylase kinase system. There is no hyperuricemia or hyperlactatemia. Type Ⅺ is characterized by hepatic glycogenosis and renal Fanconi syndrome. Type Ⅱ is a prototype of inborn lysosomal storage diseases and involves many organs but primarily the muscle. Types V and Ⅶ involve only the muscle.展开更多
Hepatocellular adenoma (HCA) is one of the important complications of glycogen storage disease type?Ia (GSD-Ia) because it can be transformed into hepatocellular carcinoma. Although surgical resection is a standard tr...Hepatocellular adenoma (HCA) is one of the important complications of glycogen storage disease type?Ia (GSD-Ia) because it can be transformed into hepatocellular carcinoma. Although surgical resection is a standard treatment of choice for solitary HCA, multiple HCAs in GSD-Ia patients present as therapeutic challenges for curative treatment. Therefore, treatment strategy according to malignant potential is important in management of HCAs in GSD-Ia. The authors present a case of histologically proven multiple HCAs without β-catenin mutations occurred in a GSD-Ia patient treated successfully with percutaneous radiofrequency ablation as a minimally invasive therapy.展开更多
Background:This study aimed to determine the effect of different carbohydrate(CHO)doses on exercise capacity in patients with McArdle disease—the paradigm of“exercise intolerance”,characterized by complete muscle g...Background:This study aimed to determine the effect of different carbohydrate(CHO)doses on exercise capacity in patients with McArdle disease—the paradigm of“exercise intolerance”,characterized by complete muscle glycogen unavailability—and to determine whether higher exogenous glucose levels affect metabolic responses at the McArdle muscle cell(in vitro)level.Methods:Patients with McArdle disease(n=8)and healthy controls(n=9)underwent a 12-min submaximal cycling constant-load bout followed by a maximal ramp test 15 min after ingesting a non-caloric placebo.In a randomized,double-blinded,cross-over design,patients repeated the tests after consuming either 75 g or 150 g of CHO(glucose:fructose=2:1).Cardiorespiratory,biochemical,perceptual,and electromyographic(EMG)variables were assessed.Additionally,glucose uptake and lactate appearance were studied in vitro in wild-type and McArdle mouse myotubes cultured with increasing glucose concentrations(0.35,1.00,4.50,and 10.00 g/L).Results:Compared with controls,patients showed the“classical”second-wind phenomenon(after prior disproportionate tachycardia,myalgia,and excess electromyographic activity during submaximal exercise,all p<0.05)and an impaired endurance exercise capacity(-51%ventilatory threshold and55%peak power output,both p<0.001).Regardless of the CHO dose(p<0.05 for both doses compared with the placebo),CHO intake increased blood glucose and lactate levels,decreased fat oxidation rates,and attenuated the second wind in the patients.However,only the higher dose increased ventilatory threshold(+27%,p=0.010)and peak power output(+18%,p=0.007).In vitro analyses revealed no differences in lactate levels across glucose concentrations in wild-type myotubes,whereas a doseresponse effect was observed in McArdle myotubes.Conclusion:CHO intake exerts beneficial effects on exercise capacity in McArdle disease,a condition associated with total muscle glycogen unavailability.Some of these benefits are dose dependent.展开更多
Glycogen accumulating organisms(GAOs) are closely related to the deterioration of enhanced biological phosphorus removal systems. However, the metabolic mechanisms that drive GAOs remain unclear. Here, the two-thirds ...Glycogen accumulating organisms(GAOs) are closely related to the deterioration of enhanced biological phosphorus removal systems. However, the metabolic mechanisms that drive GAOs remain unclear. Here, the two-thirds supernatant of a reactor were decanted following the anaerobic period to enrich GAOs. Long-term monitoring demonstrated that the system was stable and exhibited typical characteristics of GAOs metabolism. Acetate was completely consumed after 60 min of the anaerobic phase. The level of glycogen decreased from 0.20 to 0.14 g/gSS during the anaerobic phase, whereas the level of glycogen significantly increased to 0.21g/gSS at the end of the aerobic period. Moreover, there was almost no phosphate release and absorption in the complete periods, thus confirming the successful construction of a GAOs enrichment system. Microbial community analysis demonstrated that Ca. Contendobacter was among the core functional genera and showed the highest activity among all of the communities. Furthermore, our study is the first to identify the involvement of the ethyl-malonyl-CoA pathway in the synthesis of polyhydroxyvalerate via croR, ccr, ecm, mcd, mch and mcl genes. The Embden-Meyerhof-Parnas(EMP) pathway was preferentially used via glgP. Furthermore, the glyoxylate cycle was the main source of ATP under anaerobic conditions, whereas the tricarboxylic acid cycle provided ATP under aerobic conditions. aceA and mdh appeared to be major modulators of the glyoxylate pathway for controlling energy flow. Collectively, our findings not only revealed the crucial metabolic mechanisms in a GAOs enrichment system but also provided insights into the potential application of Ca. Contendobacter for wastewater treatment.展开更多
Glycogen storage diseases(GSDs),also referred to as glycogenoses,are inherited metabolic disorders of glycogen metabolism caused by deficiency of enzymes or transporters involved in the synthesis or degradation of gly...Glycogen storage diseases(GSDs),also referred to as glycogenoses,are inherited metabolic disorders of glycogen metabolism caused by deficiency of enzymes or transporters involved in the synthesis or degradation of glycogen leading to aberrant storage and/or utilization.The overall estimated GSD incidence is 1 case per 20000-43000 live births.There are over 20 types of GSD including the subtypes.This heterogeneous group of rare diseases represents inborn errors of carbohydrate metabolism and are classified based on the deficient enzyme and affected tissues.GSDs primarily affect liver or muscle or both as glycogen is particularly abundant in these tissues.However,besides liver and skeletal muscle,depending on the affected enzyme and its expression in various tissues,multiorgan involvement including heart,kidney and/or brain may be seen.Although GSDs share similar clinical features to some extent,there is a wide spectrum of clinical phenotypes.Currently,the goal of treatment is to maintain glucose homeostasis by dietary management and the use of uncooked cornstarch.In addition to nutritional interventions,pharmacological treatment,physical and supportive therapies,enzyme replacement therapy(ERT)and organ transplantation are other treatment approaches for both disease manifestations and longterm complications.The lack of a specific therapy for GSDs has prompted efforts to develop new treatment strategies like gene therapy.Since early diagnosis and aggressive treatment are related to better prognosis,physicians should be aware of these conditions and include GSDs in the differential diagnosis of patients with relevant manifestations including fasting hypoglycemia,hepatomegaly,hypertransaminasemia,hyperlipidemia,exercise intolerance,muscle cramps/pain,rhabdomyolysis,and muscle weakness.Here,we aim to provide a comprehensive review of GSDs.This review provides general characteristics of all types of GSDs with a focus on those with liver involvement.展开更多
Glycogen storage disease type Ia(GSD-Ia)is an autosomal recessive metabolic disorder caused by a deficiency in glucose-6-phosphatase-α(G6Pase-αor G6PC)that is expressed primarily in the liver,kidney,and intestine.G6...Glycogen storage disease type Ia(GSD-Ia)is an autosomal recessive metabolic disorder caused by a deficiency in glucose-6-phosphatase-α(G6Pase-αor G6PC)that is expressed primarily in the liver,kidney,and intestine.G6Pase-αcatalyzes the hydrolysis of glucose-6-phosphate(G6P)to glucose and phosphate in the terminal step of gluconeogenesis and glycogenolysis,and is a key enzyme for endogenous glucose production.The active site of G6Pase-αis inside the endoplasmic reticulum(ER)lumen.For catalysis,the substrate G6P must be translocated from the cytoplasm into the ER lumen by a G6P transporter(G6PT).The functional coupling of G6Pase-αand G6PT maintains interprandial glucose homeostasis.Dietary therapies for GSD-Ia are available,but cannot prevent the long-term complication of hepatocellular adenoma that may undergo malignant transformation to hepatocellular carcinoma.Animal models of GSD-Ia are now available and are being exploited to both delineate the disease more precisely and develop new treatment approaches,including gene therapy.展开更多
BACKGROUND Glycogen storage disease type Ib(GSD-Ib)is a glycogen metabolism disorder that leads to the manifestations of inflammatory bowel disease(IBD),especially Crohn’s disease(CD)-like colitis.Although biological...BACKGROUND Glycogen storage disease type Ib(GSD-Ib)is a glycogen metabolism disorder that leads to the manifestations of inflammatory bowel disease(IBD),especially Crohn’s disease(CD)-like colitis.Although biological agents are effective for treating CD,their application in the treatment of GSD-Ib with CD-like colitis has been rarely reported.CASE SUMMARY A 13-year-old Han male was diagnosed with GSD-Ib with CD.The patient was treated with granulocyte colony-stimulating factor.When he had symptoms of CD-like colitis,he was continuously pumped with enteral nutrition and administered oral mesalazine for 2 wk;however,the symptoms did not improve significantly.Hence,infliximab(IFX)was administered.Hitherto,the patient has been followed up for 1 year,and no clinical manifestations have been observed.After 6 mo of treatment(fifth IFX treatment),the disease activity index and all inflammatory indexes decreased,and a review of the colonoscopy data showed that the ulcers appeared smooth.CONCLUSION In this study,the patient was successfully treated with IFX.In cases of GSD-Ib,IBD should be highly considered.展开更多
BACKGROUND Glycogen storage disease type Ia(GSDIa) is an autosomal recessive inborn error of carbohydrate metabolism that is caused by deficiency of the enzyme glucose-6-phosphatase(G6Pase),leading to disturbed glycog...BACKGROUND Glycogen storage disease type Ia(GSDIa) is an autosomal recessive inborn error of carbohydrate metabolism that is caused by deficiency of the enzyme glucose-6-phosphatase(G6Pase),leading to disturbed glycogenolysis and gluconeogenesis.Patients with GSDIa show severe fasting hypoglycemia,hyperlipidemia,hyperlactacidemia,and hyperuricemia,which are associated with fatal outcomes in pregnant women and fetuses.CASE SUMMARY Herein,we report the case of a 24-year-old female who on her first visit to the hospital,presented with pregnancy combined with extremely high hyperlipidemia and hyperlactic acidosis with anemia,and frequent hypoglycemia occurred during the treatment.Genetic tests revealed a mutation in the G6Pase gene(G6PC) at 17q21,the patient was finally diagnosed with glycogen storage disease type Ia for the first time after 22 years of inaccurate treatment.She has been treated with a continuous double filtration plasmapheresis(DFPP) strategy to remove blood lipids,and a cornstarch diet therapy.The patient did not develop pancreatitis during the course of the disease and a healthy baby girl weighing 3 kg was delivered.CONCLUSION Patients with GSDIa may be misdiagnosed as epilepsy.DFPP can be used to control hyperlipidemia in GSDIa patients during pregnancy.展开更多
Hepatocellular adenomas(HCAs)represent rare,benign liver tumours occurring predominantly in females taking oral contraceptives.In children,HCAs comprise less than 5%of hepatic tumours and demonstrate association with ...Hepatocellular adenomas(HCAs)represent rare,benign liver tumours occurring predominantly in females taking oral contraceptives.In children,HCAs comprise less than 5%of hepatic tumours and demonstrate association with various conditions.The contemporary classification of HCAs,based on their distinctive genotypes and clinical phenotypes,includes hepatocyte nuclear factor 1 homeobox alpha-inactivated HCAs,beta-catenin-mutated HCAs,inflammatory HCAs,combined beta-catenin-mutated and inflammatory HCAs,sonic hedgehogactivated HCAs,and unclassified HCAs.In children,there is a lack of literature on the characteristics and distribution of HCA subtypes.In this review,we summarized different HCA subtypes and the clinicopathologic spectrum of HCAs in the paediatric population.展开更多
Metabolic liver diseases(MLD)are the second most common indication for liver transplantation(LT)in children.This is based on the fact that the majority of enzymes involved in various metabolic pathways are present wit...Metabolic liver diseases(MLD)are the second most common indication for liver transplantation(LT)in children.This is based on the fact that the majority of enzymes involved in various metabolic pathways are present within the liver and LT can cure or at least control the disease manifestation.LT is also performed in metabolic disorders for end-stage liver disease,its sequelae including hepatocellular cancer.It is also performed for preventing metabolic crisis’,arresting progression of neurological dysfunction with a potential to reverse symptoms in some cases and for preventing damage to end organs like kidneys as in the case of primary hyperoxalosis and methyl malonic acidemia.Pathological findings in explant liver with patients with metabolic disease include unremarkable liver to steatosis,cholestasis,inflammation,variable amount of fibrosis,and cirrhosis.The outcome of LT in metabolic disorders is excellent except for patients with mitochondrial disorders where significant extrahepatic involvement leads to poor outcomes and hence considered a contraindication for LT.A major advantage of LT is that in the post-operative period most patients can discontinue the special formula which they were having prior to the transplant and this increases their well-being and improves growth parameters.Auxiliary partial orthotopic LT has been described for patients with noncirrhotic MLD where a segmental graft is implanted in an orthotopic position after partial resection of the native liver.The retained native liver can be the potential target for future gene therapy when it becomes a clinical reality.展开更多
BACKGROUND Glycogen storage disease(GSD)is an autosomal recessive inborn metabolic disorder.Patients with GSD are prone to hypoglycaemia,hyperlactacidemia and bleeding.GSD type 1b(GSD-1b)patients specifically can deve...BACKGROUND Glycogen storage disease(GSD)is an autosomal recessive inborn metabolic disorder.Patients with GSD are prone to hypoglycaemia,hyperlactacidemia and bleeding.GSD type 1b(GSD-1b)patients specifically can develop neutropenia,recurrent bacterial infection and inflammatory bowel disease(IBD).Documentation of the long-term outcomes of surgical management of GSD-1b has been scarce,especially for Asian patients.We herein describe a case of GSD-1b complicated by IBD-like colitis and coloduodenal fistula.The patient was managed successfully with surgical intervention.CASE SUMMARY A 20-year-old Chinese lady confirmed by genetic testing to have GSD-1b was initially managed with uncooked cornstarch and granulocyte-colony stimulating factor.With recurrent abdominal symptoms,her condition was treated as clinical“Crohn’s disease”with mesalazine,prednisolone and azathioprine conservatively.Colonoscopy showed a tight stricture at the hepatic flexure.Subsequent computerized tomographic colonography revealed a phlegmon at the ileocaecal region with a suspected coloduodenal fistula.Eventually an exploratory laparotomy was performed and severe colitis at the ascending colon with coloduodenal fistula was confirmed.Right hemicolectomy with primary anastomosis and repair of the duodenum were performed.Surgical management of complications from GSD-1b associated IBD-like colitis has rarely been described.First-line treatment would usually be conservative.Surgical intervention like hemicolectomy is mainly reserved for refractory cases.CONCLUSION Surgical management of coloduodenal fistula in GSD-1b patients is a feasible and safe option when failed conservative management.展开更多
Brewer’s yeast strains are exposed to a spectrum of threats and“in-sults”thatcultures encounter during wort fermentation.Culture storage(including acid washing)andtheir propagation can also stress yeast systems.Str...Brewer’s yeast strains are exposed to a spectrum of threats and“in-sults”thatcultures encounter during wort fermentation.Culture storage(including acid washing)andtheir propagation can also stress yeast systems.Stresses are a plethora of parameters that ayeast culture toler-ates during its propagation,stprage,and throughout and between wortfermentations.Stress can result in a number of effects on a yeast cul-ture.These includedecreases in yeast viability and vitality,depletion of intracellular glycogen,increases intrehalose,and excretion of intra-cellular proteinase A and other proteinases,with effects onbeer foam stability.Shear of cell wall components will also occur.In addition,modification ofa culture’s flocculation characteristics can result,to-gether with the formation of unfilterablemannan-protein beer hazes,Finally,increases in respiratory deficient(petite)and other yeastmu-tants have been reported.展开更多
Combined liver and kidney transplantation(CLKT)is indicated in patients with failure of both organs,or for the treatment of end-stage chronic kidney disease(ESKD)caused by a genetic defect in the liver.The aim of the ...Combined liver and kidney transplantation(CLKT)is indicated in patients with failure of both organs,or for the treatment of end-stage chronic kidney disease(ESKD)caused by a genetic defect in the liver.The aim of the present review is to provide the most up-to-date overview of the rare conditions as indications for CLKT.They are major indications for CLKT in children.However,in some of them(e.g.,atypical hemolytic uremic syndrome or primary hyperoxaluria),CLKT may be required in adults as well.Primary hyperoxaluria is divided into three types,of which type 1 and 2 lead to ESKD.CLKT has been proven effective in renal function replacement,at the same time preventing recurrence of the disease.Nephronophthisis is associated with liver fibrosis in 5%of cases and these patients are candidates for CLKT.In alpha 1-antitrypsin deficiency,hereditary C3 deficiency,lecithin cholesterol acyltransferase deficiency and glycogen storage diseases,glomerular or tubulointerstitial disease can lead to chronic kidney disease.Liver transplantation as a part of CLKT corrects underlying genetic and consequent metabolic abnormality.In atypical hemolytic uremic syndrome caused by mutations in the genes for factor H,successful CLKT has been reported in a small number of patients.However,for this indication,CLKT has been largely replaced by eculizumab,an anti-C5 antibody.CLKT has been well established to provide immune protection of the transplanted kidney against donor-specific antibodies against class I HLA,facilitating transplantation in a highly sensitized recipient.展开更多
文摘Glycogen storage diseases （GSD） are inherited metabolic disorders of glycogen metabolism. Different hormones, including insulin, glucagon, and cortisol regulate the relationship of glycolysis, gluconeogenesis and glycogen synthesis. The overall GSD incidence is estimated 1 case per 20000-43000 live births. There are over 12 types and they are classified based on the enzyme deficiency and the affected tissue. Disorders of glycogen degradation may affect primarily the liver, the muscle, or both. Type I a involves the liver, kidney and intestine （and I b also leukocytes）, and the clinical manifestations are hepatomegaly, failure to thrive, hypoglycemia, hyperlactatemia, hyperuricemia and hyperlipidemia. Type Ilia involves both the liver and muscle, and lib solely the liver. The liver symptoms generally improve with age. Type IV usually presents in the first year of life, with hepatomegaly and growth retardation. The disease in general is progressive to cirrhosis. Type Ⅵ and Ⅳ are a heterogeneous group of diseases caused by a deficiency of the liver phosphorylase and phosphorylase kinase system. There is no hyperuricemia or hyperlactatemia. Type Ⅺ is characterized by hepatic glycogenosis and renal Fanconi syndrome. Type Ⅱ is a prototype of inborn lysosomal storage diseases and involves many organs but primarily the muscle. Types V and Ⅶ involve only the muscle.
文摘Hepatocellular adenoma (HCA) is one of the important complications of glycogen storage disease type?Ia (GSD-Ia) because it can be transformed into hepatocellular carcinoma. Although surgical resection is a standard treatment of choice for solitary HCA, multiple HCAs in GSD-Ia patients present as therapeutic challenges for curative treatment. Therefore, treatment strategy according to malignant potential is important in management of HCAs in GSD-Ia. The authors present a case of histologically proven multiple HCAs without β-catenin mutations occurred in a GSD-Ia patient treated successfully with percutaneous radiofrequency ablation as a minimally invasive therapy.
文摘为了解达里湖瓦氏雅罗鱼(Leuciscus waleckii Cyprinidae)生殖洄游过程中能量代谢和消化酶活性的变化,本研究对比了捕于达里湖和贡格尔河的瓦氏雅罗鱼血清生化参数、肝脏和肌肉组织中糖原含量、肝脏组织中转氨酶和己糖激酶活性以及肝脏和肠道组织中消化酶活性的差异;并利用实验生态学方法,研究达里湖中瓦氏雅罗鱼转入贡格尔河河水中 24 h 后其血清生化参数的响应。研究结果显示,与达里湖中瓦氏雅罗鱼相比,洄游到贡格尔河中后雅罗鱼血清葡萄糖含量显著降低(P<0.05),胆固醇含量显著升高(P<0.05),总蛋白和甘油三酯含量无显著变化;肝糖原含量极显著升高(P<0.01),肌糖原含量无显著变化;肝脏组织中谷草转氨酶活性显著降低(P<0.05),谷丙转氨酶和己糖激酶活性无显著差异;肝脏和肠道组织中纤维素酶、胃蛋白酶、胰蛋白酶和淀粉酶活性均显著升高(P<0.05)。将达里湖中瓦氏雅罗鱼转入河水中 24 h 后,其血清葡萄糖和总蛋白含量显著降低(P<0.05),而甘油三酯和胆固醇含量未见明显变化。本研究结果表明,达里湖瓦氏雅罗鱼洄游过程中以肝糖原的形式为其生殖活动储备能量;肝脏和肠道组织中消化酶活性的升高可提高鱼体对营养物质的消化吸收能力。
基金supported by a Sara Borrell postdoctoral contract granted by Instituto de Salud Carlos III(CD21/00138).PLV,DB-G and AL are funded by the Spanish Ministry of Economy and Competitiveness and Fondos Feder(Alejandro Lucia,Grant No.PI18/00139)TP is funded by the Spanish Ministry of Economy and Competitiveness and Fondos Feder(Tomas Pinos,Grant No.PI22/00201).
文摘Background:This study aimed to determine the effect of different carbohydrate(CHO)doses on exercise capacity in patients with McArdle disease—the paradigm of“exercise intolerance”,characterized by complete muscle glycogen unavailability—and to determine whether higher exogenous glucose levels affect metabolic responses at the McArdle muscle cell(in vitro)level.Methods:Patients with McArdle disease(n=8)and healthy controls(n=9)underwent a 12-min submaximal cycling constant-load bout followed by a maximal ramp test 15 min after ingesting a non-caloric placebo.In a randomized,double-blinded,cross-over design,patients repeated the tests after consuming either 75 g or 150 g of CHO(glucose:fructose=2:1).Cardiorespiratory,biochemical,perceptual,and electromyographic(EMG)variables were assessed.Additionally,glucose uptake and lactate appearance were studied in vitro in wild-type and McArdle mouse myotubes cultured with increasing glucose concentrations(0.35,1.00,4.50,and 10.00 g/L).Results:Compared with controls,patients showed the“classical”second-wind phenomenon(after prior disproportionate tachycardia,myalgia,and excess electromyographic activity during submaximal exercise,all p<0.05)and an impaired endurance exercise capacity(-51%ventilatory threshold and55%peak power output,both p<0.001).Regardless of the CHO dose(p<0.05 for both doses compared with the placebo),CHO intake increased blood glucose and lactate levels,decreased fat oxidation rates,and attenuated the second wind in the patients.However,only the higher dose increased ventilatory threshold(+27%,p=0.010)and peak power output(+18%,p=0.007).In vitro analyses revealed no differences in lactate levels across glucose concentrations in wild-type myotubes,whereas a doseresponse effect was observed in McArdle myotubes.Conclusion:CHO intake exerts beneficial effects on exercise capacity in McArdle disease,a condition associated with total muscle glycogen unavailability.Some of these benefits are dose dependent.
基金supported by the National Natural Science Foundation of China (No.51678565)the Special Fund of China (No.AWS18J004)+1 种基金the Tianjin Natural Science Foundation (Nos.19JCYBJC_(2)3800, 19JCZDJC_(3)9800)the National Key R&D Program of China (No.2018YFD0800104)。
文摘Glycogen accumulating organisms(GAOs) are closely related to the deterioration of enhanced biological phosphorus removal systems. However, the metabolic mechanisms that drive GAOs remain unclear. Here, the two-thirds supernatant of a reactor were decanted following the anaerobic period to enrich GAOs. Long-term monitoring demonstrated that the system was stable and exhibited typical characteristics of GAOs metabolism. Acetate was completely consumed after 60 min of the anaerobic phase. The level of glycogen decreased from 0.20 to 0.14 g/gSS during the anaerobic phase, whereas the level of glycogen significantly increased to 0.21g/gSS at the end of the aerobic period. Moreover, there was almost no phosphate release and absorption in the complete periods, thus confirming the successful construction of a GAOs enrichment system. Microbial community analysis demonstrated that Ca. Contendobacter was among the core functional genera and showed the highest activity among all of the communities. Furthermore, our study is the first to identify the involvement of the ethyl-malonyl-CoA pathway in the synthesis of polyhydroxyvalerate via croR, ccr, ecm, mcd, mch and mcl genes. The Embden-Meyerhof-Parnas(EMP) pathway was preferentially used via glgP. Furthermore, the glyoxylate cycle was the main source of ATP under anaerobic conditions, whereas the tricarboxylic acid cycle provided ATP under aerobic conditions. aceA and mdh appeared to be major modulators of the glyoxylate pathway for controlling energy flow. Collectively, our findings not only revealed the crucial metabolic mechanisms in a GAOs enrichment system but also provided insights into the potential application of Ca. Contendobacter for wastewater treatment.
文摘Glycogen storage diseases(GSDs),also referred to as glycogenoses,are inherited metabolic disorders of glycogen metabolism caused by deficiency of enzymes or transporters involved in the synthesis or degradation of glycogen leading to aberrant storage and/or utilization.The overall estimated GSD incidence is 1 case per 20000-43000 live births.There are over 20 types of GSD including the subtypes.This heterogeneous group of rare diseases represents inborn errors of carbohydrate metabolism and are classified based on the deficient enzyme and affected tissues.GSDs primarily affect liver or muscle or both as glycogen is particularly abundant in these tissues.However,besides liver and skeletal muscle,depending on the affected enzyme and its expression in various tissues,multiorgan involvement including heart,kidney and/or brain may be seen.Although GSDs share similar clinical features to some extent,there is a wide spectrum of clinical phenotypes.Currently,the goal of treatment is to maintain glucose homeostasis by dietary management and the use of uncooked cornstarch.In addition to nutritional interventions,pharmacological treatment,physical and supportive therapies,enzyme replacement therapy(ERT)and organ transplantation are other treatment approaches for both disease manifestations and longterm complications.The lack of a specific therapy for GSDs has prompted efforts to develop new treatment strategies like gene therapy.Since early diagnosis and aggressive treatment are related to better prognosis,physicians should be aware of these conditions and include GSDs in the differential diagnosis of patients with relevant manifestations including fasting hypoglycemia,hepatomegaly,hypertransaminasemia,hyperlipidemia,exercise intolerance,muscle cramps/pain,rhabdomyolysis,and muscle weakness.Here,we aim to provide a comprehensive review of GSDs.This review provides general characteristics of all types of GSDs with a focus on those with liver involvement.
基金This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development,National Institutes of Health(HD000912-38).
文摘Glycogen storage disease type Ia(GSD-Ia)is an autosomal recessive metabolic disorder caused by a deficiency in glucose-6-phosphatase-α(G6Pase-αor G6PC)that is expressed primarily in the liver,kidney,and intestine.G6Pase-αcatalyzes the hydrolysis of glucose-6-phosphate(G6P)to glucose and phosphate in the terminal step of gluconeogenesis and glycogenolysis,and is a key enzyme for endogenous glucose production.The active site of G6Pase-αis inside the endoplasmic reticulum(ER)lumen.For catalysis,the substrate G6P must be translocated from the cytoplasm into the ER lumen by a G6P transporter(G6PT).The functional coupling of G6Pase-αand G6PT maintains interprandial glucose homeostasis.Dietary therapies for GSD-Ia are available,but cannot prevent the long-term complication of hepatocellular adenoma that may undergo malignant transformation to hepatocellular carcinoma.Animal models of GSD-Ia are now available and are being exploited to both delineate the disease more precisely and develop new treatment approaches,including gene therapy.
基金the Digestive Medical Coordinated Development Center of Beijing Hospitals Authority,No.XXZ0505.
文摘BACKGROUND Glycogen storage disease type Ib(GSD-Ib)is a glycogen metabolism disorder that leads to the manifestations of inflammatory bowel disease(IBD),especially Crohn’s disease(CD)-like colitis.Although biological agents are effective for treating CD,their application in the treatment of GSD-Ib with CD-like colitis has been rarely reported.CASE SUMMARY A 13-year-old Han male was diagnosed with GSD-Ib with CD.The patient was treated with granulocyte colony-stimulating factor.When he had symptoms of CD-like colitis,he was continuously pumped with enteral nutrition and administered oral mesalazine for 2 wk;however,the symptoms did not improve significantly.Hence,infliximab(IFX)was administered.Hitherto,the patient has been followed up for 1 year,and no clinical manifestations have been observed.After 6 mo of treatment(fifth IFX treatment),the disease activity index and all inflammatory indexes decreased,and a review of the colonoscopy data showed that the ulcers appeared smooth.CONCLUSION In this study,the patient was successfully treated with IFX.In cases of GSD-Ib,IBD should be highly considered.
文摘BACKGROUND Glycogen storage disease type Ia(GSDIa) is an autosomal recessive inborn error of carbohydrate metabolism that is caused by deficiency of the enzyme glucose-6-phosphatase(G6Pase),leading to disturbed glycogenolysis and gluconeogenesis.Patients with GSDIa show severe fasting hypoglycemia,hyperlipidemia,hyperlactacidemia,and hyperuricemia,which are associated with fatal outcomes in pregnant women and fetuses.CASE SUMMARY Herein,we report the case of a 24-year-old female who on her first visit to the hospital,presented with pregnancy combined with extremely high hyperlipidemia and hyperlactic acidosis with anemia,and frequent hypoglycemia occurred during the treatment.Genetic tests revealed a mutation in the G6Pase gene(G6PC) at 17q21,the patient was finally diagnosed with glycogen storage disease type Ia for the first time after 22 years of inaccurate treatment.She has been treated with a continuous double filtration plasmapheresis(DFPP) strategy to remove blood lipids,and a cornstarch diet therapy.The patient did not develop pancreatitis during the course of the disease and a healthy baby girl weighing 3 kg was delivered.CONCLUSION Patients with GSDIa may be misdiagnosed as epilepsy.DFPP can be used to control hyperlipidemia in GSDIa patients during pregnancy.
文摘Hepatocellular adenomas(HCAs)represent rare,benign liver tumours occurring predominantly in females taking oral contraceptives.In children,HCAs comprise less than 5%of hepatic tumours and demonstrate association with various conditions.The contemporary classification of HCAs,based on their distinctive genotypes and clinical phenotypes,includes hepatocyte nuclear factor 1 homeobox alpha-inactivated HCAs,beta-catenin-mutated HCAs,inflammatory HCAs,combined beta-catenin-mutated and inflammatory HCAs,sonic hedgehogactivated HCAs,and unclassified HCAs.In children,there is a lack of literature on the characteristics and distribution of HCA subtypes.In this review,we summarized different HCA subtypes and the clinicopathologic spectrum of HCAs in the paediatric population.
文摘Metabolic liver diseases(MLD)are the second most common indication for liver transplantation(LT)in children.This is based on the fact that the majority of enzymes involved in various metabolic pathways are present within the liver and LT can cure or at least control the disease manifestation.LT is also performed in metabolic disorders for end-stage liver disease,its sequelae including hepatocellular cancer.It is also performed for preventing metabolic crisis’,arresting progression of neurological dysfunction with a potential to reverse symptoms in some cases and for preventing damage to end organs like kidneys as in the case of primary hyperoxalosis and methyl malonic acidemia.Pathological findings in explant liver with patients with metabolic disease include unremarkable liver to steatosis,cholestasis,inflammation,variable amount of fibrosis,and cirrhosis.The outcome of LT in metabolic disorders is excellent except for patients with mitochondrial disorders where significant extrahepatic involvement leads to poor outcomes and hence considered a contraindication for LT.A major advantage of LT is that in the post-operative period most patients can discontinue the special formula which they were having prior to the transplant and this increases their well-being and improves growth parameters.Auxiliary partial orthotopic LT has been described for patients with noncirrhotic MLD where a segmental graft is implanted in an orthotopic position after partial resection of the native liver.The retained native liver can be the potential target for future gene therapy when it becomes a clinical reality.
文摘BACKGROUND Glycogen storage disease(GSD)is an autosomal recessive inborn metabolic disorder.Patients with GSD are prone to hypoglycaemia,hyperlactacidemia and bleeding.GSD type 1b(GSD-1b)patients specifically can develop neutropenia,recurrent bacterial infection and inflammatory bowel disease(IBD).Documentation of the long-term outcomes of surgical management of GSD-1b has been scarce,especially for Asian patients.We herein describe a case of GSD-1b complicated by IBD-like colitis and coloduodenal fistula.The patient was managed successfully with surgical intervention.CASE SUMMARY A 20-year-old Chinese lady confirmed by genetic testing to have GSD-1b was initially managed with uncooked cornstarch and granulocyte-colony stimulating factor.With recurrent abdominal symptoms,her condition was treated as clinical“Crohn’s disease”with mesalazine,prednisolone and azathioprine conservatively.Colonoscopy showed a tight stricture at the hepatic flexure.Subsequent computerized tomographic colonography revealed a phlegmon at the ileocaecal region with a suspected coloduodenal fistula.Eventually an exploratory laparotomy was performed and severe colitis at the ascending colon with coloduodenal fistula was confirmed.Right hemicolectomy with primary anastomosis and repair of the duodenum were performed.Surgical management of complications from GSD-1b associated IBD-like colitis has rarely been described.First-line treatment would usually be conservative.Surgical intervention like hemicolectomy is mainly reserved for refractory cases.CONCLUSION Surgical management of coloduodenal fistula in GSD-1b patients is a feasible and safe option when failed conservative management.
文摘Brewer’s yeast strains are exposed to a spectrum of threats and“in-sults”thatcultures encounter during wort fermentation.Culture storage(including acid washing)andtheir propagation can also stress yeast systems.Stresses are a plethora of parameters that ayeast culture toler-ates during its propagation,stprage,and throughout and between wortfermentations.Stress can result in a number of effects on a yeast cul-ture.These includedecreases in yeast viability and vitality,depletion of intracellular glycogen,increases intrehalose,and excretion of intra-cellular proteinase A and other proteinases,with effects onbeer foam stability.Shear of cell wall components will also occur.In addition,modification ofa culture’s flocculation characteristics can result,to-gether with the formation of unfilterablemannan-protein beer hazes,Finally,increases in respiratory deficient(petite)and other yeastmu-tants have been reported.
文摘Combined liver and kidney transplantation(CLKT)is indicated in patients with failure of both organs,or for the treatment of end-stage chronic kidney disease(ESKD)caused by a genetic defect in the liver.The aim of the present review is to provide the most up-to-date overview of the rare conditions as indications for CLKT.They are major indications for CLKT in children.However,in some of them(e.g.,atypical hemolytic uremic syndrome or primary hyperoxaluria),CLKT may be required in adults as well.Primary hyperoxaluria is divided into three types,of which type 1 and 2 lead to ESKD.CLKT has been proven effective in renal function replacement,at the same time preventing recurrence of the disease.Nephronophthisis is associated with liver fibrosis in 5%of cases and these patients are candidates for CLKT.In alpha 1-antitrypsin deficiency,hereditary C3 deficiency,lecithin cholesterol acyltransferase deficiency and glycogen storage diseases,glomerular or tubulointerstitial disease can lead to chronic kidney disease.Liver transplantation as a part of CLKT corrects underlying genetic and consequent metabolic abnormality.In atypical hemolytic uremic syndrome caused by mutations in the genes for factor H,successful CLKT has been reported in a small number of patients.However,for this indication,CLKT has been largely replaced by eculizumab,an anti-C5 antibody.CLKT has been well established to provide immune protection of the transplanted kidney against donor-specific antibodies against class I HLA,facilitating transplantation in a highly sensitized recipient.
