Epidemiology, treatment and burden of Wilson disease in France: A 10-year analysis of the national health insurance database.

BACKGROUND & AIMS: Wilson disease (WD) is a rare hereditary, debilitating disease that is fatal if untreated. Given its low prevalence, collecting longitudinal information on large cohorts of patients is challenging. Analysis of health insurance databases offers an approach to meet this challenge. The aim of this study was to evaluate longitudinal trends in the presentation and management of patients with WD identified in the French national health insurance database (SNDS). METHODS: This retrospective, longitudinal, observational study identified people with WD in the SNDS database through hospitalisation diagnosis codes and long-term illness status between 2009 and 2019 inclusive. For each patient, data were extracted on hospitalisations, liver transplantation, mortality, WD-specific treatments (d-penicillamine, trientine and zinc), disability status and sick leave. RESULTS: 1,928 patients with WD were identified, of whom 1,520 (78.8%) were analysed. Prevalence of WD in 2019 was estimated as 2.2 cases per 100,000. Of the 670 patients first documented between 2010 and 2019, 76.1% were hospitalised at least once for a mean duration of 4.63±10.6 days. 152 patients (10.0%) underwent liver transplantation and 205 died (13.5%). The mean age at death was 57.9 ± 23.1 years. 665 patients (43.8%) received a WD-specific treatment at least once. 167 patients (17.1%) received a government disability pension and 624 (41.1%) benefited from long-term illness status due to WD. CONCLUSIONS: Unexpectedly, less than half of patients with WD received treatment recommended in practice guidelines, which may contribute to a high disease burden in terms of hospitalisations, disability and reduced life expectancy. Improving treatment rates, building patient awareness of long-term disease impact or developing a new paradigm of treatment could make a significant contribution to reducing the disease burden.

Wilson disease and other neurodegenerations with metal accumulations.

Trace elements, such as iron, copper, manganese, and calcium, which are essential constituents necessary for cellular homeostasis, become toxic when present in excess quantities. In this article, we describe disorders arising from endogenous dysregulation of metal homeostasis leading to their tissue accumulation. Although subgroups of these diseases lead to regional brain metal accumulation, mostly in globus pallidus, which is susceptible to accumulate divalent metal ions, other subgroups cause systemic metal accumulation affecting the whole brain, liver, and other parenchymal organs. The latter group comprises Wilson disease, manganese transporter deficiency, and aceruloplasminemia and responds favorably to chelation treatment.

Long-term outcomes of patients with Wilson disease in a large Austrian cohort.

BACKGROUND & AIMS: Wilson disease is an autosomal recessive disorder that affects copper metabolism, leading to copper accumulation in liver, central nervous system, and kidneys. There are few data on long-term outcomes and survival from large cohorts; we studied these features in a well-characterized Austrian cohort of patients with Wilson disease. METHODS: We analyzed data from 229 patients diagnosed with Wilson disease from 1961 through 2013; 175 regularly attended a Wilson disease outpatient clinic and/or their physicians were contacted for information on disease and treatment status and outcomes. For 53 patients lost during the follow-up period, those that died and reasons for their death were identified from the Austrian death registry. RESULTS: The mean observation period was 14.8 ± 11.4 years (range, 0.5-52.0 years), resulting in 3116 patient-years. Of the patients, 61% presented with hepatic disease, 27% with neurologic symptoms, and 10% were diagnosed by family screening at presymptomatic stages. Patients with a hepatic presentation were diagnosed younger (21.2 ± 12.0 years) than patients with neurologic disease (28.8 ± 12.0; P < .001). In 2% of patients, neither symptoms nor onset of symptoms could be determined with certainty. Most patients stabilized (35%) or improved on chelation therapy (26% fully recovered, 24% improved), but 15% deteriorated; 8% required a liver transplant, and 7.4% died within the observation period (71% of deaths were related to Wilson disease). A lower proportion of patients with Wilson disease survived for 20 years (92%) than healthy Austrians (97%), adjusted for age and sex (P = .03). Cirrhosis at diagnosis was the best predictor of death (odds ratio, 6.8; 95% confidence interval, 1.5-31.03; P = .013) and need for a liver transplant (odds ratio, 07; 95% confidence interval, 0.016-0.307; P < .001). Only 84% of patients with cirrhosis survived 20 years after diagnosis (compared with healthy Austrians, P =.008). CONCLUSION: Overall, patients who receive adequate care for Wilson disease have a good long-term prognosis. However, cirrhosis increases the risk of death and liver disease. Early diagnosis, at a precirrhotic stage, might increase survival times and reduce the need for a liver transplant.

Current state of Wilson disease patients in central Japan.

OBJECTIVE: This study evaluated the current state of patients with Wilson disease in central Japan. PATIENTS AND METHODS: Between 1999 and 2007, 30 patients were diagnosed as having Wilson disease with an International Diagnostic Score of 4 or more. The phenotypes, genotypes and post-diagnostic courses of these patients were analyzed. RESULTS: Twenty-six patients had ATP7B mutations responsible for Wilson disease. Four patients had a single mutant chromosome. There were 2 major mutations of 2333 G>T and 2871 delC (40%), and 6 novel mutations (13%) in our patients. The first clinical manifestation was the hepatic form in 22, neurological form in 5, and hemolysis in 3 patients. The hepatic form was diagnosed around the age of 13 years, followed by neurological complication with a time lag of 9 years. Thus, some patients, especially patients with the neurological form, did not undergo early diagnostic tests including ATP7B analysis. During the post-diagnosis period, 3 patients were hospitalized for recurrent liver disease, and 2 patients committed suicide. One female patient died from acute hepatic failure associated with encephalopathy after fertilization therapy, while 2 male patients recovered from encephalopathy-free, prolonged hepatic failure after noncompliance with drug therapy. The King's Scores for liver transplantation were below the cut-off in both cases. CONCLUSION: To minimize delayed diagnosis, ceruloplasmin determination and ATP7B analysis may be recommended to patients showing hepatic damage of unknown etiology. At gene diagnosis, appropriate management of patients including compliance education and emotional care to prevent suicide might be important.

Triethylene tetramine dihydrochloride (trientine) in children with Wilson disease: experience at King's College Hospital and review of the literature.

Our aim was to review our experience of trientine as chelation therapy in children with Wilson disease (WD) and compare to that reported in the literature. We made a retrospective review of the medical notes of 16 of 96 (17%) children diagnosed with WD between 1981 and 2006. Children were 6.6 to 15 years old. Only three received trientine as initial therapy [parental choice (two), allergic reactions to penicillamine (one) during the penicillamine challenge], 13 of 16 were converted from penicillamine to trientine because of reactions to penicillamine: haematuria in four, bone marrow suppression in three, neutropenia in three. Trientine was discontinued in three due to allergic rash, low copper excretion and one with compliance problems requiring transplantation. Seventy-five per cent of children presented with chronic liver disease. Kayser-Fleischer rings were noticed in eight of 16, Wilson Ferenci score range was between 4 and 10 (nl < 4). Laboratory indices remained relatively stable. In line with previous reports, trientine was used mainly as secondary treatment when there were severe side effects with penicillamine. Whilst the current evidence is low quality, it appears that trientine is as efficacious as penicillamine and small population studies show a lower side effect profile.