The underlying pathophysiology of liver dysfunction in urea cycle disorders(UCDs) is still largely elusive. There is some evidence that the accumulation of urea cycle(UC) intermediates are toxic for hepatocyte mitocho...The underlying pathophysiology of liver dysfunction in urea cycle disorders(UCDs) is still largely elusive. There is some evidence that the accumulation of urea cycle(UC) intermediates are toxic for hepatocyte mitochondria. It is possible that liver injury is directly caused by the toxicity of ammonia. The rarity of UCDs, the lack of checking of iron level in these patients, superficial knowledge of UC and an underestimation of the metabolic role of fumaric acid, are the main reasons that are responsible for the incomprehension of the mechanism of liver injury in patients suffering from UCDs. Owing to our routine clinical practice to screen for iron overload in severely ill neonates, with the focus on the newborns suffering from acute liver failure, we report a case of citrullinemia with neonatal liver failure and high blood parameters of iron overload. We hypothesize that the key is in the decreased-deficient fumaric acid production in the course of UC in UCDs that causes several sequentially intertwined metabolic disturbances with final result of liver iron overload. The presented hypothesis could be easily tested by examining the patients suffering from UCDs, for liver iron overload. This could be easily performed in countries with a high population and comprehensive national register for inborn errors of metabolism. Conclusion: Providing the hypothesis is correct, neonatal liver damage in patients having UCD can be prevented by the supplementation of pregnant women with fumaric or succinic acid, prepared in the form of iron supplementation pills. After birth, liverdamage in patients having UCDs can be prevented by supplementation of these patients with zinc fumarate or zinc succinylate, as well.展开更多
Familial pancreatic cancer(FPC)is broadly defined as two first-degree-relatives with pancreatic cancer(PC)and accounts for 4%-10%of PC.Several genetic syndromes,including Peutz-Jeghers syndrome,hereditary pancreatitis...Familial pancreatic cancer(FPC)is broadly defined as two first-degree-relatives with pancreatic cancer(PC)and accounts for 4%-10%of PC.Several genetic syndromes,including Peutz-Jeghers syndrome,hereditary pancreatitis,hereditary breast-ovarian cancer syndrome(HBOC),Lynch syndrome,and familial adenomatous polyposis(FAP),also have increased risks of PC,but the narrowest definition of FPC excludes these known syndromes.When compared with other familial tumors,proven genetic alterations are limited to a small proportion(<20%)and the familial aggregation is usually modest.However,an ethnic deviation(Ashkenazi Jewish>Caucasian)and a younger onset are common also in FPC.In European countries,"anticipation"is reported in FPC families,as with other hereditary syndromes;a trend toward younger age and worse prognosis is recognized in the late years.The resected pancreases of FPC kindred often show multiple pancreatic intraepithelial neoplasia(Pan IN)foci,with various K-ras mutations,similar to colorectal polyposis seen in the FAP patients.As with HBOC patients,a patient who is a BRCA mutation carrier with unresectable pancreatic cancer(accounting for 0%-19%of FPC patients)demonstrated better outcome following platinum and Poly(ADP-ribose)polymerase inhibitor treatment.Western countries have established FPC registries since the 1990 s and several surveillance projects for highrisk individuals are now ongoing to detect early PCs.Improvement in lifestyle habits,including non-smoking,is recommended for individuals at risk.In Japan,the FPC study group was initiated in 2013 and the Japanese FPC registry was established in 2014 by the Japan Pancreas Society.展开更多
文摘The underlying pathophysiology of liver dysfunction in urea cycle disorders(UCDs) is still largely elusive. There is some evidence that the accumulation of urea cycle(UC) intermediates are toxic for hepatocyte mitochondria. It is possible that liver injury is directly caused by the toxicity of ammonia. The rarity of UCDs, the lack of checking of iron level in these patients, superficial knowledge of UC and an underestimation of the metabolic role of fumaric acid, are the main reasons that are responsible for the incomprehension of the mechanism of liver injury in patients suffering from UCDs. Owing to our routine clinical practice to screen for iron overload in severely ill neonates, with the focus on the newborns suffering from acute liver failure, we report a case of citrullinemia with neonatal liver failure and high blood parameters of iron overload. We hypothesize that the key is in the decreased-deficient fumaric acid production in the course of UC in UCDs that causes several sequentially intertwined metabolic disturbances with final result of liver iron overload. The presented hypothesis could be easily tested by examining the patients suffering from UCDs, for liver iron overload. This could be easily performed in countries with a high population and comprehensive national register for inborn errors of metabolism. Conclusion: Providing the hypothesis is correct, neonatal liver damage in patients having UCD can be prevented by the supplementation of pregnant women with fumaric or succinic acid, prepared in the form of iron supplementation pills. After birth, liverdamage in patients having UCDs can be prevented by supplementation of these patients with zinc fumarate or zinc succinylate, as well.
文摘Familial pancreatic cancer(FPC)is broadly defined as two first-degree-relatives with pancreatic cancer(PC)and accounts for 4%-10%of PC.Several genetic syndromes,including Peutz-Jeghers syndrome,hereditary pancreatitis,hereditary breast-ovarian cancer syndrome(HBOC),Lynch syndrome,and familial adenomatous polyposis(FAP),also have increased risks of PC,but the narrowest definition of FPC excludes these known syndromes.When compared with other familial tumors,proven genetic alterations are limited to a small proportion(<20%)and the familial aggregation is usually modest.However,an ethnic deviation(Ashkenazi Jewish>Caucasian)and a younger onset are common also in FPC.In European countries,"anticipation"is reported in FPC families,as with other hereditary syndromes;a trend toward younger age and worse prognosis is recognized in the late years.The resected pancreases of FPC kindred often show multiple pancreatic intraepithelial neoplasia(Pan IN)foci,with various K-ras mutations,similar to colorectal polyposis seen in the FAP patients.As with HBOC patients,a patient who is a BRCA mutation carrier with unresectable pancreatic cancer(accounting for 0%-19%of FPC patients)demonstrated better outcome following platinum and Poly(ADP-ribose)polymerase inhibitor treatment.Western countries have established FPC registries since the 1990 s and several surveillance projects for highrisk individuals are now ongoing to detect early PCs.Improvement in lifestyle habits,including non-smoking,is recommended for individuals at risk.In Japan,the FPC study group was initiated in 2013 and the Japanese FPC registry was established in 2014 by the Japan Pancreas Society.
