BACKGROUND Wilson's disease(WD)is a rare inherited disorder of copper metabolism.Treatment consists of chelating agents,but side effects are common.We describe a patient who developed colitis during trientine trea...BACKGROUND Wilson's disease(WD)is a rare inherited disorder of copper metabolism.Treatment consists of chelating agents,but side effects are common.We describe a patient who developed colitis during trientine treatment leading to decompensation of liver cirrhosis.CASE SUMMARY A healthy 51-year-old woman was diagnosed with liver cirrhosis due to decompensation with ascites.Etiologic evaluation raised suspicion of hereditary hemochromatosis because of compound heterozygosity HFE p.C282Y/p.H63D,and phlebotomy was started.Re-evaluation showed low ceruloplasmin,increased urinary copper excretion and the presence of Kayser-Fleischer rings.WD was confirmed by genetic analysis.Because of decompensated cirrhosis,she was referred for liver transplant evaluation.Simultaneously,treatment with trientine was initiated.Liver function initially stabilized,and the patient was not accepted for a liver transplant.Shortly after this,she developed severe hemorrhagic colitis,most probably a side effect of trientine.During that episode,she decompensated with hepatic encephalopathy.Because of a second decompensating event,she was accepted for liver transplantation,and an uneventful transplantation was carried out after clinical improvement of colitis.CONCLUSION Despite WD being a rare disorder,it is important to consider because it can present with a plethora of symptoms from childhood to an elderly age.Colitis should be recognized as a serious adverse drug reaction to trientine treatment that can result in decompensated liver disease.展开更多
BACKGROUND Wilson's disease(WD)is a rare metabolic disorder of copper accumulation in organs such as liver,brain,and cornea.Diagnoses and treatments are challenging in settings,where advanced diagnostic tests are ...BACKGROUND Wilson's disease(WD)is a rare metabolic disorder of copper accumulation in organs such as liver,brain,and cornea.Diagnoses and treatments are challenging in settings,where advanced diagnostic tests are unavailable,copper chelating agents are frequently scarce,healthcare professionals lack disease awareness,and medical follow-ups are limited.Prompt diagnoses and treatments help prevent complications,improve patients’quality of life,and ensure a normal life expectancy.The clinical presentations and outcomes of WD can vary within a single family.CASE SUMMARY We present the cases of two siblings(19 and 27 years)from a consanguineous family in rural Ecuador,diagnosed as having WD during a family screening.The male patient,diagnosed at age 19 after his brother’s death from acute liver failure,presented with compensated cirrhosis,neurological symptoms,and bilateral Kayser-Fleischer rings.He developed progressive neurological deterioration during an irregular treatment with D-penicillamine due to medication shortages.His condition improved upon switching to trientine tetrahydrochloride,and his neurological symptoms improved over an 8-year period of follow-ups.The female patient,diagnosed at age 10,exhibited only biochemical alterations.Her treatment history was similar;however,she remained asymptomatic without disease progression over the same follow-up period.We discuss the potential influence of epigenetic mechanisms and modifier genes on the various phenotypes,emphasizing the need for research in these areas to optimize therapeutic strategies.CONCLUSION Our patients’medical histories show how early diagnosis and treatment can prevent disease progression;and,how suboptimal treatments impact disease outcomes.展开更多
Wilson disease is an autosomal recessive disorder affecting the ATP7B gene located on chromosome 13q.This leads to copper deposition in various organs,most importantly in the liver and brain.The genetic mutations are ...Wilson disease is an autosomal recessive disorder affecting the ATP7B gene located on chromosome 13q.This leads to copper deposition in various organs,most importantly in the liver and brain.The genetic mutations are vast,well reported in the West but poorly documented in developing countries.Hence the diagnosis is made with a constellation of clinico-laboratory parameters which have significant overlap with other liver diseases and often pose a significant dilemma for clinicians.Diagnostic scoring systems are not fool-proof.The availability and affordability of chelators in developing countries impact the drug compliance of patients.While D-penicillamine is a potent drug,its side effects lead to drug discontinuation.Trientine is cost-prohibitive in developing countries.There is no single test to assess the adequacy of chelation.Exchangeable urinary copper is an essential upcoming diagnostic and prognostic tool.In the presence of cirrhosis,hypersplenism clouds the assessment of myelosuppression of drugs.Similarly,it may be difficult to distinguish disease tubulopathy from druginduced glomerulonephritis.Neurological worsening due to chelators may appear similar to disease progression.Presentation as fulminant hepatic failure requires rapid workup.There is a limited window of opportunity to salvage these patients with the help of plasmapheresis and other liver-assisted devices.This review addresses the challenges and clinical dilemmas faced at beside in developing countries.展开更多
Wilson’s disease(WD)is a rare inherited disorder of human copper metabolism,with an estimated prevalence of 1:30000-1:50000 and a broad spectrum of hepatic and neuropsychiatric manifestations.In healthy individuals,t...Wilson’s disease(WD)is a rare inherited disorder of human copper metabolism,with an estimated prevalence of 1:30000-1:50000 and a broad spectrum of hepatic and neuropsychiatric manifestations.In healthy individuals,the bile is the main route of elimination of copper.In WD patients,copper accumulates in the liver,it is released into the bloodstream,and is excreted in urine.Copper can also be accumulated in the brain,kidneys,heart,and osseous matter and causes damage due to direct toxicity or oxidative stress.Hepatic WD is commonly but not exclusively diagnosed in childhood or young adulthood.Adherent,non-cirrhotic WD patients seem to have a normal life expectancy.Nevertheless,chronic management of patients with Wilson’s disease is challenging,as available biochemical tests have many limitations and do not allow a clear identification of non-compliance,overtreatment,or treatment goals.To provide optimal care,clinicians should have a complete understanding of these limitations and counterbalance them with a thorough clinical assessment.The aim of this review is to provide clinicians with practical tools and suggestions which may answer doubts that can arise during chronic management of patients with hepatic WD.In particular,it summarises current knowledge on Wilson’s disease clinical and biochemical monitoring and treatment.It also analyses available evidence on pregnancy and the role of low-copper diet in WD.Future research should focus on trying to provide new copper metabolism tests which could help to guide treatment adjustments.展开更多
Chelation is the mainstay of therapy in certain pediatric liver diseases.Copper and iron related disorders require chelation.Wilson’s disease(WD),one of the common causes of cirrhosis in children is treated primarily...Chelation is the mainstay of therapy in certain pediatric liver diseases.Copper and iron related disorders require chelation.Wilson’s disease(WD),one of the common causes of cirrhosis in children is treated primarily with copper chelating agents like D-penicillamine and trientine.D-Penicillamine though widely used due its high efficacy in hepatic WD is fraught with frequent adverse effects resulting discontinuation.Trientine,an alternative drug has comparable efficacy in hepatic WD but has lower frequency of adverse effects.The role of ammonium tetra-thiomolybdate is presently experimental in hepatic WD.Indian childhood cirrhosis is related to excessive copper ingestion,rarely seen in present era.DPenicillamine is effective in the early part of this disease with reversal of clinical status.Iron chelators are commonly used in secondary hemochromatosis of liver in hemolytic anemias.There are strict chelation protocols during bone marrow transplant.The role of iron chelation in neonatal hemochromatosis is presently not in vogue due to its poor efficacy and availability of other modalities of therapy.Hereditary hemochromatosis is rare in children and the use of iron chelators in this condition is limited.展开更多
Wilson disease is an autosomal recessive disorder of copper metabolism.Diagnosis depends primarily on clinical features,biochemical parameters and the presence of the Kayser-Fleischer ring.Genetic analysis for mutatio...Wilson disease is an autosomal recessive disorder of copper metabolism.Diagnosis depends primarily on clinical features,biochemical parameters and the presence of the Kayser-Fleischer ring.Genetic analysis for mutations within ATP7B is a convincing diagnostic tool.The traditional treatment for WD includes chelation of excessive copper accumulation and reduction of copper intake.Medical therapy is effective but WD is not yet curable.Liver transplantation is especially helpful for patients who fail to respond to medical therapy or present with fulminant liver failure,although evaluation of its long-term effect are still in need.展开更多
文摘BACKGROUND Wilson's disease(WD)is a rare inherited disorder of copper metabolism.Treatment consists of chelating agents,but side effects are common.We describe a patient who developed colitis during trientine treatment leading to decompensation of liver cirrhosis.CASE SUMMARY A healthy 51-year-old woman was diagnosed with liver cirrhosis due to decompensation with ascites.Etiologic evaluation raised suspicion of hereditary hemochromatosis because of compound heterozygosity HFE p.C282Y/p.H63D,and phlebotomy was started.Re-evaluation showed low ceruloplasmin,increased urinary copper excretion and the presence of Kayser-Fleischer rings.WD was confirmed by genetic analysis.Because of decompensated cirrhosis,she was referred for liver transplant evaluation.Simultaneously,treatment with trientine was initiated.Liver function initially stabilized,and the patient was not accepted for a liver transplant.Shortly after this,she developed severe hemorrhagic colitis,most probably a side effect of trientine.During that episode,she decompensated with hepatic encephalopathy.Because of a second decompensating event,she was accepted for liver transplantation,and an uneventful transplantation was carried out after clinical improvement of colitis.CONCLUSION Despite WD being a rare disorder,it is important to consider because it can present with a plethora of symptoms from childhood to an elderly age.Colitis should be recognized as a serious adverse drug reaction to trientine treatment that can result in decompensated liver disease.
文摘BACKGROUND Wilson's disease(WD)is a rare metabolic disorder of copper accumulation in organs such as liver,brain,and cornea.Diagnoses and treatments are challenging in settings,where advanced diagnostic tests are unavailable,copper chelating agents are frequently scarce,healthcare professionals lack disease awareness,and medical follow-ups are limited.Prompt diagnoses and treatments help prevent complications,improve patients’quality of life,and ensure a normal life expectancy.The clinical presentations and outcomes of WD can vary within a single family.CASE SUMMARY We present the cases of two siblings(19 and 27 years)from a consanguineous family in rural Ecuador,diagnosed as having WD during a family screening.The male patient,diagnosed at age 19 after his brother’s death from acute liver failure,presented with compensated cirrhosis,neurological symptoms,and bilateral Kayser-Fleischer rings.He developed progressive neurological deterioration during an irregular treatment with D-penicillamine due to medication shortages.His condition improved upon switching to trientine tetrahydrochloride,and his neurological symptoms improved over an 8-year period of follow-ups.The female patient,diagnosed at age 10,exhibited only biochemical alterations.Her treatment history was similar;however,she remained asymptomatic without disease progression over the same follow-up period.We discuss the potential influence of epigenetic mechanisms and modifier genes on the various phenotypes,emphasizing the need for research in these areas to optimize therapeutic strategies.CONCLUSION Our patients’medical histories show how early diagnosis and treatment can prevent disease progression;and,how suboptimal treatments impact disease outcomes.
文摘Wilson disease is an autosomal recessive disorder affecting the ATP7B gene located on chromosome 13q.This leads to copper deposition in various organs,most importantly in the liver and brain.The genetic mutations are vast,well reported in the West but poorly documented in developing countries.Hence the diagnosis is made with a constellation of clinico-laboratory parameters which have significant overlap with other liver diseases and often pose a significant dilemma for clinicians.Diagnostic scoring systems are not fool-proof.The availability and affordability of chelators in developing countries impact the drug compliance of patients.While D-penicillamine is a potent drug,its side effects lead to drug discontinuation.Trientine is cost-prohibitive in developing countries.There is no single test to assess the adequacy of chelation.Exchangeable urinary copper is an essential upcoming diagnostic and prognostic tool.In the presence of cirrhosis,hypersplenism clouds the assessment of myelosuppression of drugs.Similarly,it may be difficult to distinguish disease tubulopathy from druginduced glomerulonephritis.Neurological worsening due to chelators may appear similar to disease progression.Presentation as fulminant hepatic failure requires rapid workup.There is a limited window of opportunity to salvage these patients with the help of plasmapheresis and other liver-assisted devices.This review addresses the challenges and clinical dilemmas faced at beside in developing countries.
文摘Wilson’s disease(WD)is a rare inherited disorder of human copper metabolism,with an estimated prevalence of 1:30000-1:50000 and a broad spectrum of hepatic and neuropsychiatric manifestations.In healthy individuals,the bile is the main route of elimination of copper.In WD patients,copper accumulates in the liver,it is released into the bloodstream,and is excreted in urine.Copper can also be accumulated in the brain,kidneys,heart,and osseous matter and causes damage due to direct toxicity or oxidative stress.Hepatic WD is commonly but not exclusively diagnosed in childhood or young adulthood.Adherent,non-cirrhotic WD patients seem to have a normal life expectancy.Nevertheless,chronic management of patients with Wilson’s disease is challenging,as available biochemical tests have many limitations and do not allow a clear identification of non-compliance,overtreatment,or treatment goals.To provide optimal care,clinicians should have a complete understanding of these limitations and counterbalance them with a thorough clinical assessment.The aim of this review is to provide clinicians with practical tools and suggestions which may answer doubts that can arise during chronic management of patients with hepatic WD.In particular,it summarises current knowledge on Wilson’s disease clinical and biochemical monitoring and treatment.It also analyses available evidence on pregnancy and the role of low-copper diet in WD.Future research should focus on trying to provide new copper metabolism tests which could help to guide treatment adjustments.
文摘Chelation is the mainstay of therapy in certain pediatric liver diseases.Copper and iron related disorders require chelation.Wilson’s disease(WD),one of the common causes of cirrhosis in children is treated primarily with copper chelating agents like D-penicillamine and trientine.D-Penicillamine though widely used due its high efficacy in hepatic WD is fraught with frequent adverse effects resulting discontinuation.Trientine,an alternative drug has comparable efficacy in hepatic WD but has lower frequency of adverse effects.The role of ammonium tetra-thiomolybdate is presently experimental in hepatic WD.Indian childhood cirrhosis is related to excessive copper ingestion,rarely seen in present era.DPenicillamine is effective in the early part of this disease with reversal of clinical status.Iron chelators are commonly used in secondary hemochromatosis of liver in hemolytic anemias.There are strict chelation protocols during bone marrow transplant.The role of iron chelation in neonatal hemochromatosis is presently not in vogue due to its poor efficacy and availability of other modalities of therapy.Hereditary hemochromatosis is rare in children and the use of iron chelators in this condition is limited.
文摘Wilson disease is an autosomal recessive disorder of copper metabolism.Diagnosis depends primarily on clinical features,biochemical parameters and the presence of the Kayser-Fleischer ring.Genetic analysis for mutations within ATP7B is a convincing diagnostic tool.The traditional treatment for WD includes chelation of excessive copper accumulation and reduction of copper intake.Medical therapy is effective but WD is not yet curable.Liver transplantation is especially helpful for patients who fail to respond to medical therapy or present with fulminant liver failure,although evaluation of its long-term effect are still in need.
