Screening and Diagnosis of Wilson’s Disease in Pediatric Patients

Indications for Screening

All first‑degree relatives (siblings, children, parents) of a newly diagnosed Wilson’s disease patient should be screened irrespective of symptoms, because presymptomatic treatment can prevent disease manifestations and provide near‑normal longevity. 1, 2, 3
Any child who presents with clinical features of autoimmune hepatitis must be evaluated for Wilson’s disease; this is a Class I, Level B recommendation since autoimmune hepatitis and Wilson’s disease are clinically and histologically indistinguishable in younger patients. 1, 4, 3
Children with findings consistent with non‑alcoholic fatty liver disease or steatohepatitis should also be screened for Wilson’s disease. 4, 3
A pediatric patient with fulminant hepatic failure together with Coombs‑negative hemolytic anemia, modest aminotransferase elevation (typically < 2000 IU/L), low alkaline phosphatase (typically < 40 IU/L) and an alkaline phosphatase‑to‑bilirubin ratio < 2 is highly characteristic of Wilson’s disease and warrants immediate investigation. 2, 4, 5, 3

When the ATP7B mutation(s) or haplotype of the index case are known, molecular testing of first‑degree relatives is the most efficient primary screening strategy and is now considered the standard approach for asymptomatic siblings. 4, 3

In individuals without Kayser‑Fleischer rings who have subnormal ceruloplasmin and abnormal liver tests, a liver biopsy with quantitative hepatic copper measurement should be performed; a hepatic copper concentration > 250 µg/g dry weight is diagnostic for Wilson’s disease. 2, 4, 3

If the initial family screening is normal, repeat screening should be considered after 2–5 years to capture late‑onset disease. 4, 3

All individuals identified as patients by family screening who are older than 3–4 years should receive treatment promptly to achieve optimal outcomes. 1, 2, 4, 3

Measuring ceruloplasmin in dried‑blood spots shows promise for newborn detection of Wilson’s disease, but further methodological refinement is required before widespread implementation. 4, 3

The American Association for the Study of Liver Diseases recommends that Wilson disease should be suspected in any individual between ages 3 and 55 years with liver abnormalities of uncertain cause, and age alone should never exclude the diagnosis 6, 7
The European Association for the Study of the Liver suggests that Wilson disease presenting as fulminant hepatic failure has a characteristic pattern that distinguishes it from other causes and carries 95% mortality without liver transplantation 6, 8

The American Association for the Study of Liver Diseases states that hepatic manifestations that should trigger evaluation include asymptomatic elevation of aminotransferases, asymptomatic hepatomegaly or isolated splenomegaly, clinical picture resembling acute viral hepatitis, and presentation mimicking autoimmune hepatitis 6, 7, 8
The European Association for the Study of the Liver recommends that neuropsychiatric manifestations warranting investigation include tremor with characteristic "wing beating" appearance, dysarthria, dystonia, and "juvenile Parkinsonism" 9, 10
The American Association for the Study of Liver Diseases suggests that other presentations that should raise suspicion include Coombs-negative hemolytic anemia, renal abnormalities, premature osteoporosis or arthritis, cardiomyopathy, and menstrual irregularities 6, 7, 8, 9

The American Association for the Study of Liver Diseases recommends a comprehensive diagnostic workup including slit-lamp examination, serum ceruloplasmin, 24-hour urinary copper excretion, serum copper and non-ceruloplasmin copper calculation, liver function tests, complete blood count, and liver biopsy with quantitative hepatic copper measurement 6, 7
The European Association for the Study of the Liver suggests that genetic testing for ATP7B mutations can support diagnosis but should not be used alone 11

The American Association for the Study of Liver Diseases states that untreated Wilson disease is universally fatal, but with appropriate treatment, prolonged survival has become the norm 9, 12
The European Association for the Study of the Liver recommends treatment options including chelating agents and zinc salts, and urgent liver transplantation for fulminant hepatic failure or end-stage liver disease 6, 9, 13

The American Association for the Study of Liver Diseases suggests that first-degree relatives of any newly diagnosed patient must be screened for Wilson disease, as presymptomatic treatment prevents disease manifestations entirely 6