Management of Wilson Disease Diagnosed in Infancy

Abstract

Increased access to molecular genetic testing is changing the demographics for diagnosing inherited disorders and imposing new challenges for medical management. Wilson disease (WD), typically diagnosed in older children and adults, can now be detected in utero and in infants (children younger than 24 months, including neonates) via genetic testing. An evidence-based approach to management of these neonates and extremely young children, who are typically asymptomatic, has been hampered by lack of clinical experience. We present a case of an infantile diagnosis of WD, review available experience, and discuss current trends in antenatal genetic testing of parents and fetus that may lead to a very early diagnosis of WD. Based on physiological and nutritional considerations, we propose an algorithmic approach to management of infantile WD as a starting point for further discussion. Future collaboration amongst specialists is essential to identify evidence-based approaches and best practice for managing treatment of infants with genetically diagnosed WD.

Low Copper Diet—A Therapeutic Option for Wilson Disease?

“…Therefore, zinc is used primarily in very young children identified by family screening or in adult patients who have already been well detoxified with chelating agents. In the published case reports with infantile WD, additional zinc therapy was usually started in the second year of life in order to avoid copper accumulation in the hepatocytes [ 23 ]. However, the exact time to start zinc therapy is uncertain.…”

A multidisciplinary approach to the diagnosis and management of Wilson disease: Executive summary of the 2022 Practice Guidance on Wilson disease from the American Association for the Study of Liver Diseases

“…[257,258] Diagnosis in the neonatal period also permits timely treatment. [259,260] Guidance statement 14 14. First-degree relatives of patients newly diagnosed with WD must be screened for WD.…”

“…Zinc appears preferable for these very young asymptomatic children, but there is no consensus as to whether treatment should be started without evidence of organ damage because of possible adverse effects of treatment on development. [260]…”

“…[341] Intake of breastmilk in the first year of life can range anywhere from 480-1020 ml/day (16-34 oz/day), bringing copper intake to 0.19-0.41 mg/day, which is 96%-204% of the AI. [260] If breastmilk is not an option, infant formulas provide an appropriate alternative with average copper content ranging slightly higher than breastmilk at 0.4-0.6 mg/L, thus bringing average copper intake to 0.18-0.57mg/day on standard formula (90%-285% of the AI) (Appendix S2). Partially and fully hydrolyzed formulas run slightly higher still but may be necessary based on gastrointestinal tolerance.…”

Designing Clinical Trials in Wilson’s Disease

“…Treatment will aim to prevent development of injury and disease. ( 16 ) Drug selection and age for treatment initiation is unclear and require further study.…”