Wilson's disease in Sardinian population: The experience of a pediatric referral center.

Loudianos, Georgios; Satta, Stefania; Lepori, Maria B.; Anni, Franco; Balloi, Roberta; Soddu, Consolata; Fenu, Maria L.; Lilliu, Franco; Nurchi, Anna M.; De Virgiliis, Stefano

Background and Objectives: Wilson's disease (WD) in children and adolescents is predominantly asymptomatic or oligo‐symptomatic. The symptoms are nonspecific and difficult to distinguish from other hepatic or neuropsychiatric disorders. In this study, we present the experience of a pediatric referral center for WD diagnosis and treatment. Patients and Methods: We retrospectively analyzed clinical and laboratory data from 99 patients with WD of Sardinian origin, including physical examination, laboratory biochemical testing, liver biopsy, and genetic analysis. Results: Patients were prevalently oligo‐symptomatic or asymptomatic. The median age of diagnosis was 8.78 years. Ceruloplasmin values were lower than normal values in all analyzed patients. Twenty‐four‐hour urinary copper levels were higher than 40 μg/24‐h in 92/96 patients. In all analyzed patients with the exception of one, liver copper was higher than 250 μg/g of dry weight but all had >75 μg/g of dry weight. Statistical analysis showed correlation between the age at diagnosis, serum copper, and 24‐h urinary copper. Correlation was also found between serum copper and 24‐h urinary copper. Molecular analysis of ATP7B gene allowed complete characterization in all the analyzed patients. Conclusion: A high index of clinical suspicion and biochemical tests including liver tests, serum ceruloplasmin, and basal 24‐h urinary copper excretion and genotype determination are key to WD diagnosis. The long experience that a referral center for WD possesses is an important factor in making WD diagnosis a more accurate process. Studies in animal models on WD could be used as a guide to further investigate the molecular mechanisms that regulate copper metabolism and influence the natural history of WD. What is Known: Wilson's disease (WD) in children and adolescents is prevalently asymptomatic or oligo‐symptomatic.Symptoms are nonspecific and are difficult to distinguish from other hepatic or neuropsychiatric disorders. What is New: This study demonstrates a significant correlation between increasing age and levels of noncerulopasmin‐bound copper during childhood and adolescence.This study brings further evidence to the correlation between increasing age and 24‐h urinary copper levels during childhood and adolescence.The study demonstrates a significant correlation between serum and 24‐h urinary copper levels.This study reports strong evidence for liver Cu accumulation prevalently during early pediatric age and adolescence.

HEPATOLENTICULAR degeneration; NEUROBEHAVIORAL disorders; LIVER biopsy; CERULOPLASMIN; ADOLESCENCE

Journal of Pediatric Gastroenterology & Nutrition, 2024, Vol 79, Issue 4, p807

0277-2116

Academic Journal

10.1002/jpn3.12343