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Deguti MM, Araujo FC, Terrabuio DRB, Araujo TF, Barbosa ER, Porta G, Cançado ELR. Wilson disease: the diagnostic challenge and treatment outcomes in a series of 262 cases. ARQUIVOS DE NEURO-PSIQUIATRIA 2024; 82:1-9. [PMID: 38811021 DOI: 10.1055/s-0044-1786855] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/31/2024]
Abstract
BACKGROUND Wilson disease (WD) is an autosomal recessive disorder that leads to organ toxicity due to copper overload. Early diagnosis is complicated by the rarity and diversity of manifestations. OBJECTIVE To describe the diagnostic features and response to treatment in our cohort of WD patients. METHODS This was a retrospective analysis of 262 WD patients stratified by clinical presentation, complementary exams, ATP7B genotyping, and response to treatment. RESULTS Symptoms occurred at an average age of 17.4 (7-49) years, and patients were followed up for an average of 9.6 (0-45) years. Patients presented mainly with hepatic (36.3%), neurologic (34.7%), and neuropsychiatric (8.3%) forms. Other presentations were hematologic, renal, or musculoskeletal, and 16.8% of the patients were asymptomatic. Kayser-Fleischer rings occurred in 78.3% of the patients, hypoceruloplasminemia in 98.3%, and elevated cupruria/24h in 73.0%, with an increase after D-penicillamine in 54.0%. Mutations of the ATP7B gene were detected in 84.4% of alleles. Brain magnetic resonance imaging showed abnormalities in the basal ganglia in 77.7% of patients. D-penicillamine was the first choice in 93.6% of the 245 patients, and 21.1% of these patients were switched due to adverse effects. The second-line therapies were zinc and trientine. The therapeutic response did not differ significantly between the drugs (p = 0.2). Nine patients underwent liver transplantation and 82 died. CONCLUSION Wilson disease is diagnosed at a late stage, and therapeutic options are limited. In people under 40 years of age with compatible manifestations, WD could be considered earlier in the differential diagnosis. There is a need to include ATP7B genotyping and therapeutic alternatives in clinical practice.
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Affiliation(s)
- Marta Mitiko Deguti
- Universidade de São Paulo, Faculdade de Medicina, Departamento de Gastroenterologia, São Paulo SP, Brazil
- Universidade de São Paulo, Faculdade de Medicina, Instituto de Medicina Tropical, Laboratório de Gastroenterologia e Hepatologia, São Paulo SP, Brazil
| | - Fabiana Cordeiro Araujo
- Universidade de São Paulo, Faculdade de Medicina, Departamento de Gastroenterologia, São Paulo SP, Brazil
| | | | - Thiago Ferreira Araujo
- Universidade de São Paulo, Faculdade de Medicina, Instituto de Medicina Tropical, Laboratório de Gastroenterologia e Hepatologia, São Paulo SP, Brazil
| | - Egberto Reis Barbosa
- Universidade de São Paulo, Faculdade de Medicina, Departamento de Neurologia, São Paulo SP, Brazil
| | - Gilda Porta
- Universidade de São Paulo, Faculdade de Medicina, Departamento de Pediatria, São Paulo SP, Brazil
| | - Eduardo Luiz Rachid Cançado
- Universidade de São Paulo, Faculdade de Medicina, Departamento de Gastroenterologia, São Paulo SP, Brazil
- Universidade de São Paulo, Faculdade de Medicina, Instituto de Medicina Tropical, Laboratório de Gastroenterologia e Hepatologia, São Paulo SP, Brazil
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Lynch EN, Campani C, Innocenti T, Dragoni G, Forte P, Galli A. Practical insights into chronic management of hepatic Wilson’s disease. World J Clin Cases 2022; 10:4334-4347. [PMID: 35663095 PMCID: PMC9125272 DOI: 10.12998/wjcc.v10.i14.4334] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Revised: 10/07/2021] [Accepted: 03/26/2022] [Indexed: 02/06/2023] Open
Abstract
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.
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Affiliation(s)
- Erica Nicola Lynch
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Claudia Campani
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
- Department of Experimental and Clinical Medicine, University of Florence, Florence 50134, Italy
| | - Tommaso Innocenti
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Gabriele Dragoni
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
- Department of Medical Biotechnologies, University of Siena, Siena 53100, Italy
| | - Paolo Forte
- Division of Gastroenterology, University Hospital “Careggi”, Florence 50134, Italy
| | - Andrea Galli
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
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Di Dato F, Spadarella S, Puoti MG, Caprio MG, Pagliardini S, Zuppaldi C, Vallone G, Fecarotta S, Esposito G, Iorio R, Parenti G, Spagnuolo MI. Daily Fructose Traces Intake and Liver Injury in Children with Hereditary Fructose Intolerance. Nutrients 2019; 11:2397. [PMID: 31591370 PMCID: PMC6835214 DOI: 10.3390/nu11102397] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2019] [Revised: 09/23/2019] [Accepted: 10/02/2019] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Hereditary fructose intolerance (HFI) is a rare genetic disorder of fructose metabolism due to aldolase B enzyme deficiency. Treatment consists of fructose, sorbitol, and sucrose (FSS)-free diet. We explore possible correlations between daily fructose traces intake and liver injury biomarkers on a long-term period, in a cohort of young patients affected by HFI. METHODS Patients' clinical data and fructose daily intake were retrospectively collected. Correlations among fructose intake, serum alanine aminotransferase (ALT) level, carbohydrate-deficient transferrin (CDT) percentage, liver ultrasonography, genotype were analyzed. RESULTS We included 48 patients whose mean follow-up was 10.3 ± 5.6 years and fructose intake 169 ± 145.4 mg/day. Eighteen patients had persistently high ALT level, nine had abnormal CDT profile, 45 had signs of liver steatosis. Fructose intake did not correlate with ALT level nor with steatosis severity, whereas it correlated with disialotransferrin percentage (R2 0.7, p < 0.0001) and tetrasialotransferrin/disialotransferrin ratio (R2 0.5, p = 0.0001). p.A150P homozygous patients had lower ALT values at diagnosis than p.A175D variant homozygotes cases (58 ± 55 IU/L vs. 143 ± 90 IU/L, p = 0.01). CONCLUSION A group of HFI patients on FSS-free diet presented persistent mild hypertransaminasemia which did not correlate with fructose intake. Genotypes may influence serum liver enzyme levels. CDT profile represents a good marker to assess FSS intake.
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Affiliation(s)
- Fabiola Di Dato
- Department of Translational Medical Science, section of Pediatrics, University of Naples Federico II, 80131 Naples, Italy.
- Italian Society of Pediatric Gastroenterology and Nutrition (SIGENP), 20126 Milan, Italy.
| | - Simona Spadarella
- Department of Translational Medical Science, section of Pediatrics, University of Naples Federico II, 80131 Naples, Italy.
| | - Maria Giovanna Puoti
- Great Ormond Street Hospital for Children NHS Foundation Trust, Great Ormond St, Holborn, London WC1N 3JH, UK.
| | - Maria Grazia Caprio
- Institute of Biostructure and Bioimaging National Research Council, 80145 Naples, Italy.
| | - Severo Pagliardini
- Department of Pediatrics and Public Health and Pediatric Sciences, University of Torino, 10126 Torino, Italy.
| | - Claudia Zuppaldi
- Department of Translational Medical Science, section of Pediatrics, University of Naples Federico II, 80131 Naples, Italy.
| | - Gianfranco Vallone
- Pediatric Radiology, Department of Advanced Biomedical Sciences, University of Naples Federico II, 80131 Naples, Italy.
| | - Simona Fecarotta
- Department of Translational Medical Science, section of Pediatrics, University of Naples Federico II, 80131 Naples, Italy.
| | - Gabriella Esposito
- Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, Italy.
- CEINGE Advanced Biotechnologies, 80145 Naples, Italy.
| | - Raffaele Iorio
- Department of Translational Medical Science, section of Pediatrics, University of Naples Federico II, 80131 Naples, Italy.
- Italian Society of Pediatric Gastroenterology and Nutrition (SIGENP), 20126 Milan, Italy.
| | - Giancarlo Parenti
- Department of Translational Medical Science, section of Pediatrics, University of Naples Federico II, 80131 Naples, Italy.
- Telethon Institute of Genetics and Medicine, 80078 Pozzuoli, Italy.
| | - Maria Immacolata Spagnuolo
- Department of Translational Medical Science, section of Pediatrics, University of Naples Federico II, 80131 Naples, Italy.
- Italian Society of Pediatric Gastroenterology and Nutrition (SIGENP), 20126 Milan, Italy.
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Hadžić N, Deheragoda M, Dhawan A. Managing pre-symptomatic Wilson disease in genetic era - More questions than answers. Clin Res Hepatol Gastroenterol 2017; 41:626-628. [PMID: 28330624 DOI: 10.1016/j.clinre.2017.02.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2016] [Revised: 01/21/2017] [Accepted: 02/02/2017] [Indexed: 02/04/2023]
Affiliation(s)
- Nedim Hadžić
- Paediatric Centre for Hepatology, Gastroenterology and Nutrition, King's College Hospital, Denmark Hill, London SE5 9RS, UK.
| | | | - Anil Dhawan
- Paediatric Centre for Hepatology, Gastroenterology and Nutrition, King's College Hospital, Denmark Hill, London SE5 9RS, UK
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Ranucci G, Polishchuck R, Iorio R. Wilson's disease: Prospective developments towards new therapies. World J Gastroenterol 2017; 23:5451-5456. [PMID: 28852304 PMCID: PMC5558108 DOI: 10.3748/wjg.v23.i30.5451] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2017] [Revised: 04/11/2017] [Accepted: 07/22/2017] [Indexed: 02/06/2023] Open
Abstract
Wilson's disease (WD) is an autosomal recessive disorder of copper metabolism, caused by mutations in the ATP7B gene. A clear demand for novel WD treatment strategies has emerged. Although therapies using zinc salts and copper chelators can effectively cure WD, these drugs exhibit limitations in a substantial pool of WD patients who develop intolerance and/or severe side effects. Several lines of research have indicated intriguing potential for novel strategies and targets for development of new therapies. Here, we review these new approaches, which comprise correction of ATP7B mutants and discovery of new compounds that circumvent ATP7B-deficiency, as well as cell and gene therapies. We also discuss whether and when these new therapeutic strategies will be translated into clinical use, according to the key requirements for clinical trials that remain to be met. Finally, we discuss the hope for the current rapidly developing research on molecular mechanisms underlying WD pathogenesis and for the related potential therapeutic targets to provide a solid foundation for the next generation of WD therapies that may lead to an effective, tolerable and safe cure.
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El-Karaksy H, Fahmy M, El-Raziky MS, El-Hawary M, El-Sayed R, El-Koofy N, El-Mougy F, El-Hennawy A, El-Shabrawi M. A clinical study of Wilson's disease: The experience of a single Egyptian Paediatric Hepatology Unit. Arab J Gastroenterol 2011; 12:125-130. [PMID: 22055589 DOI: 10.1016/j.ajg.2011.07.007] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2011] [Revised: 07/08/2011] [Accepted: 07/28/2011] [Indexed: 01/06/2023]
Abstract
BACKGROUND AND STUDY AIMS Most paediatric patients with Wilson's disease (WD) present with hepatic manifestations, but some may have neurologic or psychiatric features. Our aim was to define the clinical, biochemical features and the outcome of therapy of a group of Egyptian children diagnosed with WD. PATIENTS AND METHODS The study was carried out at the Paediatric Hepatology Unit at Cairo University Children's Hospital, Egypt; 54 patients were diagnosed with WD from 1996 to 2009. The diagnosis was based on low serum ceruloplasmin levels, increased urinary copper concentrations before or after D-penicillamine challenge and/or the presence of Kayser-Fleischer (K-F) rings. RESULTS The clinical presentation was as follows: hepatic presentation in 33 patients (61%), hepato-neurologic 3 (5.5%), neurologic 5 (9.3%) and presymptomatic 13 (24%). Twelve couples had more than one affected sib. Increased urinary copper concentrations before or after D-penicillamine challenge was found in all patients, low serum ceruloplasmin in 97% and K-F rings in 31.5%. All patients were treated with penicillamine and zinc sulphate except one presymptomatic case who was treated with zinc sulphate only. Three patients underwent liver transplantation and eight patients died after a median duration of treatment of 6 months (1-36). The hepatic symptoms improved with treatment but the neurological symptoms remained stationary. CONCLUSIONS Clinical and biochemical assays remain the standard for diagnosis of WD. Penicillamine and zinc therapy can effectively treat WD with hepatic symptoms. Liver transplantation remains life saving for those with fulminant and end stage WD. Screening for presymptomatic sibs is of utmost importance.
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Cope-Yokoyama S, Finegold MJ, Sturniolo GC, Kim K, Mescoli C, Rugge M, Medici V. Wilson disease: Histopathological correlations with treatment on follow-up liver biopsies. World J Gastroenterol 2010; 16:1487-94. [PMID: 20333789 PMCID: PMC2846254 DOI: 10.3748/wjg.v16.i12.1487] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
AIM: To investigate the progression of hepatic histopathology in serial liver biopsies from Wilson disease (WD) patients.
METHODS: We report a group of 12 WD patients treated with zinc and/or penicillamine who underwent multiple follow-up liver biopsies. Demographic, clinical and laboratory data were gathered and all patients underwent an initial biopsy and at least one repeat biopsy.
RESULTS: Time to repeat biopsy ranged from 2 to 12 years. Six patients (non-progressors) showed stable hepatic histology or improvement. In one case, we observed improvement of fibrosis from stage 2 to 0. Six patients (progressors) had worsening of fibrosis. There was no significant correlation between the histological findings and serum aminotransferases or copper metabolism parameters. The hepatic copper concentration reached normal levels in only two patients: one from the non-progressors and one from the progressors group. The estimated rate of progression of hepatic fibrosis in the entire group was 0 units per year in the time frame between the first and the second liver biopsy (4 years), and 0.25 between the second and the third (3 years). In the progressors group, the rate of progression of liver fibrosis was estimated at 0.11 fibrosis units per year between the first and second biopsy and, 0.6 fibrosis units between the second and third biopsy.
CONCLUSION: The inability of clinical tools to detect fibrosis progression in WD suggests that a liver biopsy with hepatic copper quantification every 3 years should be considered.
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Nicastro E, Loudianos G, Zancan L, D'Antiga L, Maggiore G, Marcellini M, Barbera C, Marazzi MG, Francavilla R, Pastore M, Vajro P, D'Ambrosi M, Vegnente A, Ranucci G, Iorio R. Genotype-phenotype correlation in Italian children with Wilson's disease. J Hepatol 2009; 50:555-561. [PMID: 19118915 DOI: 10.1016/j.jhep.2008.09.020] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2008] [Revised: 09/23/2008] [Accepted: 09/30/2008] [Indexed: 12/13/2022]
Abstract
BACKGROUND/AIMS Wilson's disease phenotype is very variable for clinical and laboratory features. Our aim was to assess the role of the type of ATP7B disease causing mutations on Wilson's disease phenotype. METHODS We retrospectively evaluated the data of children with Wilson's disease from eight pediatric departments. RESULT Fifty-eight patients (34 male, median age at diagnosis 7.4 years) from 47 unrelated families were studied, carrying 34 different mutations. The most common mutations were the missense p.H1069Q and p.M769V, the nonsense p.R1319X, the frameshift c.2299delC, c.2298_2299insC and c.2530delA, and the splice site mutation c.2447+5G>A. Serum ceruloplasmin and copper were lower among the patients' homozygotes for nonsense and frameshift mutations than in patients with missense mutations. A normalization of serum alanine aminotransferase after therapy was not achieved in 23.6% of patients with missense mutations versus 45.5% of patients with nonsense/frameshift mutations. A direct linear correlation was found between age at diagnosis and urinary copper excretion at diagnosis. CONCLUSIONS The type of mutation explains at least a part of Wilson's disease phenotype, and mutation analysis should be considered as an integrative tool for such a challenging diagnosis. Urinary copper excretion appears to be correlated to the age at diagnosis rather than genotype.
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Affiliation(s)
- Emanuele Nicastro
- Department of Pediatrics, University of Naples Federico II, Naples, Italy
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Medici V, Rossaro L, Sturniolo GC. Wilson disease--a practical approach to diagnosis, treatment and follow-up. Dig Liver Dis 2007; 39:601-9. [PMID: 17382611 DOI: 10.1016/j.dld.2006.12.095] [Citation(s) in RCA: 67] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2006] [Revised: 12/12/2006] [Accepted: 12/23/2006] [Indexed: 12/11/2022]
Abstract
Wilson disease is an inherited, autosomal recessive, copper accumulation and toxicity disorder that affects about 30 individuals per million. This rare disease is caused by mutations in the gene encoding a copper-transporting P-type ATPase, which is important for copper excretion into bile, leading to copper accumulation in the liver. Toxic copper concentrations can also be found in the brain and kidney, and clinical phenotypes include hepatic, haemolytic, neurologic and psychiatric diseases. Diagnosis is based on the combination of clinical features and findings such as increased urinary copper excretion, reduced levels of serum ceruloplasmin, high concentrations of copper in liver tissues and Kayser-Fleischer rings. Genetic studies are also becoming available for clinical use, but the utility of direct mutation analysis is limited. Wilson disease can be treated, and early diagnosis is essential: the goal of therapy is to reduce copper accumulation either by enhancing its urinary excretion or by decreasing its intestinal absorption. Medical therapies include penicillamine, trientine, zinc and tetrathiomolibdate. Liver transplantation is a relatively successful treatment option when medical therapy fails or in case of acute liver failure, even though it is also characterized by short- and long-term complications.
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Affiliation(s)
- V Medici
- Department of Surgical and Gastroenterological Sciences, Gastroenterology Section, Via Giustiniani 2, University Hospital of Padova, 35128 Padova, Italy
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Medici V, Trevisan CP, D'Incà R, Barollo M, Zancan L, Fagiuoli S, Martines D, Irato P, Sturniolo GC. Diagnosis and management of Wilson's disease: results of a single center experience. J Clin Gastroenterol 2006; 40:936-941. [PMID: 17063115 DOI: 10.1097/01.mcg.0000225670.91722.59] [Citation(s) in RCA: 99] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
AIMS To report on the diagnostic features, management, and clinical outcome after different treatments of Wilson's disease patients followed over a mean period of 15 years. PATIENTS Thirty-five patients with Wilson's disease referred to the University of Padova's Department of Gastroenterology for diagnosis or treatment were observed for a mean 15 years. The diagnosis was based on clinical symptoms, laboratory tests (ceruloplasmin, urinary, and hepatic copper concentrations), and uptake of the radiostable isotope Cu into the plasma protein pool. Hepatic Cu content was measured by regular follow-up biopsies. Neurologic outcome after therapy was assessed using a newly developed scoring system. RESULTS Twenty-three (65.7%) patients presented with liver disease; 12 (34.3%) had mixed neurologic and hepatic involvement. All patients had been initially treated with either penicillamine (23) or zinc sulfate (12). The neurologic symptoms became worse or remained stationary in 75% of those treated with penicillamine, whereas zinc treatment improved these symptoms in 90% of treated cases. Both treatments were effective in improving the hepatic symptoms. No differences in hepatic Cu content emerged between follow-up biopsies in either treatment group. Six patients (26%) had to abandon the penicillamine treatment due to side effects. In all, 4 patients underwent liver transplantation, which was successful in 3, with a mean survival after transplantation of 4.6 years; the fourth, who had a severe neurologic impairment, died of central pontine myelinolysis. CONCLUSIONS Penicillamine and zinc can effectively treat Wilson's disease, though the side effects of penicillamine may be severe enough to prompt its suspension. Liver transplantation remains the treatment of choice for end-stage liver disease.
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Affiliation(s)
- Valentina Medici
- Department of Surgical and Gastroenterological Sciences, Section of Gastroenterology, University of Padova, Italy
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Abstract
PURPOSE OF REVIEW The purpose of this review is to identify and discuss recent findings related to inherited metabolic disorders of the liver that increase our understanding of the pathophysiology and treatment for hemochromatosis and other iron overload disorders, Wilson disease and alpha one antitrypsin deficiency. RECENT FINDINGS The main theme in the recent discoveries for both iron overload disorders and Wilson disease is our increasing understanding that the phenotypic expression of these disorders are greatly influenced by genes involved in the metabolic pathways for these metals, or influence the progression of liver disease independent of metal metabolism. For example, the role of hepcidin dysregulation in hemochromatosis has been a surprising discovery that provides some mechanistic understanding for the increased iron absorption that is present in this disorder. SUMMARY Given the recent explosion of information on iron and copper metabolism and the cellular processing of alpha one antitrypsin, the highlights reviewed in this article will help the reader keep up to date with the current understanding of these diseases and potential future approaches to their treatment.
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Affiliation(s)
- Michael L Schilsky
- Department of Medicine, Center for Liver Disease and Transplantation, Weill Cornell Medical Center, New York, NY 10021, USA.
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