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

J Pediatr Gastroenterol Nutr. 2024 Oct;79(4):807-817. doi: 10.1002/jpn3.12343. Epub 2024 Aug 7.

Abstract

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.

Keywords: ATP7B; diagnosis; hepatic; neuropsychiatric; urinary copper.

MeSH terms

  • Adenosine Triphosphatases / genetics
  • Adolescent
  • Cation Transport Proteins / genetics
  • Ceruloplasmin* / analysis
  • Ceruloplasmin* / metabolism
  • Child
  • Child, Preschool
  • Copper* / blood
  • Copper* / metabolism
  • Copper* / urine
  • Copper-Transporting ATPases* / genetics
  • Female
  • Hepatolenticular Degeneration* / blood
  • Hepatolenticular Degeneration* / diagnosis
  • Hepatolenticular Degeneration* / genetics
  • Humans
  • Italy
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Referral and Consultation
  • Retrospective Studies

Substances

  • Copper
  • Ceruloplasmin
  • Copper-Transporting ATPases
  • ATP7B protein, human
  • Adenosine Triphosphatases
  • Cation Transport Proteins

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