Perceptions of frailty pathway implementation in an acute setting among healthcare professionals: a qualitative study using the CFIR 2.0.

Wilson’s disease (WD) is a rare autosomal recessive disorder of copper metabolism caused by pathogenic mutations in the ATP7B gene, which encodes a copper-transporting P-type ATPase []. Defective ATP7B function leads to excessive copper accumulation, primarily in the liver and brain, resulting in progressive hepatic and neurological damage. The global prevalence of WD is estimated to be between 1 in 30,000 and 1 in 50,000 []. However, recent studies suggest that the prevalence of WD may be underestimated [–]. WD manifests with hepatic, neurological, and psychiatric symptoms, which may appear individually or in combination, with variations across different age groups and sexes []. Hepatic involvement, often the earliest symptom, is more common in younger patients and may progress to cirrhosis and liver failure in advanced cases [, ]. Neurological symptoms typically emerge between the ages of 20 and 30, with some evidence suggesting an earlier onset and greater severity in males [–]. Psychiatric symptoms often occur with neurological manifestations but may also present as the initial clinical features [, ]. Additionally, excess copper deposition can contribute to renal, hematologic, cardiac, musculoskeletal, and endocrine abnormalities [, ]. ATP7B gene locates on the long arm of chromosome 13 (13q14.3), spanning approximately 85 kb and comprising 21 exons and 20 introns. It encodes an eight-transmembrane-domain protein composed of 1465 amino acids, which is localized to the trans-Golgi network (TGN) [–]. In hepatocytes, ATP7B facilitates the incorporation of copper into newly synthesized ceruloplasmin in the TGN and mediates copper excretion into bile when intracellular copper levels rise. Dysfunction of ATP7B function leads to the abnormal deposition of copper in the body. Excess copper triggers oxidative stress, mitochondrial dysfunction, disruption of gene regulation, and apoptosis []. Currently, over 1000 mutations, including substitutions, insertions, deletions, and duplications, have been identified in the ATP7B gene []. The distribution of ATP7B mutations differs among populations and geographic regions. The p.H1069Q (c.3202 A > C) and p.R778L (c.2333G > T) mutations, located in exons 14 and 8, respectively, are the most common pathogenic mutations in European and Asian populations [].