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
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 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
Glycogen storage disease type Ia (GSD-Ia; also called von Gierke disease) is an autosomal recessive disorder of carbohydrate metabolism caused by glucose-6-phosphatase deficiency. There have been many reports describi...Glycogen storage disease type Ia (GSD-Ia; also called von Gierke disease) is an autosomal recessive disorder of carbohydrate metabolism caused by glucose-6-phosphatase deficiency. There have been many reports describing hepatic tumors in GSD patients; however, most of these reports were of hepatocellular adenomas, whereas there are only few reports describing focal nodular hyperplasia (FNH) or hepatocellular carcinoma (HCC). We report a case with GSD-Ia who had undergone a partial resection of the liver for FNH at 18 years of age and in whom moderately differentiated HCC had developed. Preoperative imaging studies, including ultrasonography, dynamic computer tomography (CT) and magnetic resonance imaging, revealed benign and malignant features. In particular, fluorodeoxyglucose-positron emission tomography (FDG-PET)/CT revealed the atypical findings that FDG accumulated at high levels in the non-tumorous hepatic parenchyma and low levels in the tumor. Right hemihepatectomy was performed. During the perioperative period, high-dose glucose and sodium bicarbonate were administered to control metabolic acidosis. He had multiple recurrences of HCC at 10 mo after surgery and was followed-up with transcatheter arterial chemoembolization. The tumor was already highly advanced when it was found by chance; therefore, a careful follow-up should be mandatory for GSD-I patients as they are at a high risk for HCC, similar to hepatitis patients.展开更多
BACKGROUND: Glycogen storage disease (GSD) is an inherited metabolic disorder in which the concentration and/or structure of glycogen in tissues is abnormal. Essentially, abnormalities in all known enzymes involved in...BACKGROUND: Glycogen storage disease (GSD) is an inherited metabolic disorder in which the concentration and/or structure of glycogen in tissues is abnormal. Essentially, abnormalities in all known enzymes involved in the synthesis or degradation of glycogen and glucose have been found to cause some type of GSD. Liver and muscle have abundant quantities of glycogen and are the most common and seriously affected tissues. This study was to assess reduced-size liver transplantation for the treatment of GSD. METHODS: The clinical data from one case of GSD type I with hepatic adenoma was retrospectively analyzed. The clinical manifestations were hepatomegaly, delayed puberty, growth retardation, sexual immaturity, hypoglycemia, and lactic acidosis, which made the young female patient eligible for reduced-size liver transplantation. RESULTS: The patient recovered uneventfully with satisfactory outcome, including 12 cm growth in height and 5 kg increase in weight during 16 months after successful reduced-size liver transplantation. She has been living a normal life for 4 years so far. CONCLUSIONS: Reduced-size liver transplantation is an effective treatment for GSD with hepatomegaly and hepatic adenoma. Delayed puberty, growth retardation, hypoglycemia and lactic acidosis can be cured by surgery.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
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
BACKGROUND Inflammatory bowel disease(IBD)is rare in patients with glycogen storage disease(GSD).In GSD patients,a decrease in the number of neutrophils leads to prolonged intestinal infection,leading to the formation...BACKGROUND Inflammatory bowel disease(IBD)is rare in patients with glycogen storage disease(GSD).In GSD patients,a decrease in the number of neutrophils leads to prolonged intestinal infection,leading to the formation of chronic inflammation and eventually the development of IBD.Minimally invasive surgery for patients with IBD has been proven to reduce inflammatory responses and postoperative risks and ultimately promote rapid recovery.Herein we discuss minimally invasive surgery and the perioperative management in a patient with GSD and IBD.CASE SUMMARY A 23-year-old male had GSD Ib associated with IBD-like disease for 10 years.Despite standard treatments,such as mesalazine,prednisone and adalimumab,the patient eventually developed colonic stenosis with incomplete ileus.After adequate assessment,the patient was treated with minimally invasive surgery and discharged in stable condition.CONCLUSION Minimally invasive surgery for patients with IBD and GSD is safe,feasible and effective.展开更多
BACKGROUND Hepatocellular adenomas are rare tumors that can occur in patients with glycogen storage disease type I.CASE SUMMARY We herein report two cases of histologically proven hepatocellular adenomas in patients w...BACKGROUND Hepatocellular adenomas are rare tumors that can occur in patients with glycogen storage disease type I.CASE SUMMARY We herein report two cases of histologically proven hepatocellular adenomas in patients with glycogen storage disease type I.Magnetic resonance imaging(MRI)was performed after bolus injection of gadoxetate disodium,a liver-specific gadolinium-based MRI contrast agent.In the present cases,some of the hepatocellular adenomas showed unexpectedly a“bull’s eye”appearance on T2-weighted and post-contrast images,which was not previously described as imaging findings of hepatocellular adenomas in glycogen storage disease.A bull’s eye appearance on T2-weighted images can be encountered in both benign(i.e.,abscess)or malignant(i.e.,epithelioid hemangioendothelioma,cholangiocarcinoma,and metastases)hepatic lesions.CONCLUSION We present two cases of hepatocellular adenomas in patients with glycogen storage disease type 1,in which gadoxetate disodium-MRI showed atypical imaging findings for hepatocellular adenomas.At present there is no systematic study evaluating MRI findings of hepatocellular adenomas in patients with glycogen storage disease,further studies are needed to specifically investigate this issue.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
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
Pompe disease (PD) is a rare inborn error of metabolism due to an abnormal acid alpha-glucosidase (GAA) activity that comprises glycogen breakdown mainly in the lysosomes. Since the introduction of enzyme replacement ...Pompe disease (PD) is a rare inborn error of metabolism due to an abnormal acid alpha-glucosidase (GAA) activity that comprises glycogen breakdown mainly in the lysosomes. Since the introduction of enzyme replacement therapy (ERT), with recombinant human GAA for the early onset PD patient, a relevant field of clinical research due to the benefits regarding survival rate has been widely documented worldwide. Objective: To describe the clinical characteristics and the ERT effects in a series of Brazilian patients with infantile onset PD (IOPD) under ERT. Methods: Brazilian patients diagnosed with IOPD under ERT were recruited through their physicians participating in the International Pompe Disease Registry from 2009 to 2017. Data were collected by an online survey. Results: 10 IOPD patients were identified through the survey with a death rate of 30% and technology dependency rate reported as 80% (motor, respiratory or nutritional fields) of the patients. After the third year of ERT, motor disabilities were lost in 50% of ambulated patients. The overall characteristics were similar to international studies. Conclusion: Despite ERT benefits in cardiac involvement, motor disabilities seem to be much more compromised in IOPD patients, with high technology dependence, especially after three years of age.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
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.
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Glycogen storage disease type Ia (GSD-Ia; also called von Gierke disease) is an autosomal recessive disorder of carbohydrate metabolism caused by glucose-6-phosphatase deficiency. There have been many reports describing hepatic tumors in GSD patients; however, most of these reports were of hepatocellular adenomas, whereas there are only few reports describing focal nodular hyperplasia (FNH) or hepatocellular carcinoma (HCC). We report a case with GSD-Ia who had undergone a partial resection of the liver for FNH at 18 years of age and in whom moderately differentiated HCC had developed. Preoperative imaging studies, including ultrasonography, dynamic computer tomography (CT) and magnetic resonance imaging, revealed benign and malignant features. In particular, fluorodeoxyglucose-positron emission tomography (FDG-PET)/CT revealed the atypical findings that FDG accumulated at high levels in the non-tumorous hepatic parenchyma and low levels in the tumor. Right hemihepatectomy was performed. During the perioperative period, high-dose glucose and sodium bicarbonate were administered to control metabolic acidosis. He had multiple recurrences of HCC at 10 mo after surgery and was followed-up with transcatheter arterial chemoembolization. The tumor was already highly advanced when it was found by chance; therefore, a careful follow-up should be mandatory for GSD-I patients as they are at a high risk for HCC, similar to hepatitis patients.
文摘BACKGROUND: Glycogen storage disease (GSD) is an inherited metabolic disorder in which the concentration and/or structure of glycogen in tissues is abnormal. Essentially, abnormalities in all known enzymes involved in the synthesis or degradation of glycogen and glucose have been found to cause some type of GSD. Liver and muscle have abundant quantities of glycogen and are the most common and seriously affected tissues. This study was to assess reduced-size liver transplantation for the treatment of GSD. METHODS: The clinical data from one case of GSD type I with hepatic adenoma was retrospectively analyzed. The clinical manifestations were hepatomegaly, delayed puberty, growth retardation, sexual immaturity, hypoglycemia, and lactic acidosis, which made the young female patient eligible for reduced-size liver transplantation. RESULTS: The patient recovered uneventfully with satisfactory outcome, including 12 cm growth in height and 5 kg increase in weight during 16 months after successful reduced-size liver transplantation. She has been living a normal life for 4 years so far. CONCLUSIONS: Reduced-size liver transplantation is an effective treatment for GSD with hepatomegaly and hepatic adenoma. Delayed puberty, growth retardation, hypoglycemia and lactic acidosis can be cured by surgery.
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BACKGROUND Inflammatory bowel disease(IBD)is rare in patients with glycogen storage disease(GSD).In GSD patients,a decrease in the number of neutrophils leads to prolonged intestinal infection,leading to the formation of chronic inflammation and eventually the development of IBD.Minimally invasive surgery for patients with IBD has been proven to reduce inflammatory responses and postoperative risks and ultimately promote rapid recovery.Herein we discuss minimally invasive surgery and the perioperative management in a patient with GSD and IBD.CASE SUMMARY A 23-year-old male had GSD Ib associated with IBD-like disease for 10 years.Despite standard treatments,such as mesalazine,prednisone and adalimumab,the patient eventually developed colonic stenosis with incomplete ileus.After adequate assessment,the patient was treated with minimally invasive surgery and discharged in stable condition.CONCLUSION Minimally invasive surgery for patients with IBD and GSD is safe,feasible and effective.
文摘BACKGROUND Hepatocellular adenomas are rare tumors that can occur in patients with glycogen storage disease type I.CASE SUMMARY We herein report two cases of histologically proven hepatocellular adenomas in patients with glycogen storage disease type I.Magnetic resonance imaging(MRI)was performed after bolus injection of gadoxetate disodium,a liver-specific gadolinium-based MRI contrast agent.In the present cases,some of the hepatocellular adenomas showed unexpectedly a“bull’s eye”appearance on T2-weighted and post-contrast images,which was not previously described as imaging findings of hepatocellular adenomas in glycogen storage disease.A bull’s eye appearance on T2-weighted images can be encountered in both benign(i.e.,abscess)or malignant(i.e.,epithelioid hemangioendothelioma,cholangiocarcinoma,and metastases)hepatic lesions.CONCLUSION We present two cases of hepatocellular adenomas in patients with glycogen storage disease type 1,in which gadoxetate disodium-MRI showed atypical imaging findings for hepatocellular adenomas.At present there is no systematic study evaluating MRI findings of hepatocellular adenomas in patients with glycogen storage disease,further studies are needed to specifically investigate this issue.
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.
文摘Pompe disease (PD) is a rare inborn error of metabolism due to an abnormal acid alpha-glucosidase (GAA) activity that comprises glycogen breakdown mainly in the lysosomes. Since the introduction of enzyme replacement therapy (ERT), with recombinant human GAA for the early onset PD patient, a relevant field of clinical research due to the benefits regarding survival rate has been widely documented worldwide. Objective: To describe the clinical characteristics and the ERT effects in a series of Brazilian patients with infantile onset PD (IOPD) under ERT. Methods: Brazilian patients diagnosed with IOPD under ERT were recruited through their physicians participating in the International Pompe Disease Registry from 2009 to 2017. Data were collected by an online survey. Results: 10 IOPD patients were identified through the survey with a death rate of 30% and technology dependency rate reported as 80% (motor, respiratory or nutritional fields) of the patients. After the third year of ERT, motor disabilities were lost in 50% of ambulated patients. The overall characteristics were similar to international studies. Conclusion: Despite ERT benefits in cardiac involvement, motor disabilities seem to be much more compromised in IOPD patients, with high technology dependence, especially after three years of age.
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.
