title: Population screening for Wilson's disease.
abstract: Wilson's disease is an autosomal recessive disorder of copper transport caused by mutations in the gene encoding an ATPase, ATP7B. Early detection of Wilson's disease is critical because effective medical treatments such as chelating agents and zinc salts are available, which can prevent lifelong neurological disabilities and/or cirrhosis. It is unfortunate that most patients are brought to our attention after they have developed serious complications such as brain damage or cirrhosis, despite the availability of effective treatments. The diagnosis is usually made through copper measurement in the liver tissue, followed by confirmation with genetic testing of the ATP7B gene. Currently, there are no effective biomarkers or methods suitable for newborn screening for Wilson's disease. Ceruloplasmin has been tested for pediatric and newborn screening with limited outcome. Recently, liquid chromatography-multiple reaction monitoring-mass spectrometry (LC-MRM-MS) has emerged as a robust technology that may enable multiplex quantification of signature proteotypic peptides with low abundance. The application of this technology may help facilitate the research on Wilson's disease for protein expression, biomarker study, diagnosis, and, hopefully, screening.
authors.affiliation: Department of Pediatrics, University of Washington School of Medicine, Seattle Children's Hospital, Seattle, Washington.
authors.forename: Si Houn
authors.initials: SH
authors.lastname: Hahn
mesh_terms: D000251:Adenosine Triphosphatases / Q000097:blood / Q000235:genetics; D000293:Adolescent; D015415:Biomarkers / Q000097:blood; D027682:Cation Transport Proteins / Q000097:blood / Q000235:genetics; D002570:Ceruloplasmin / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D002853:Chromatography, Liquid / Q000379:methods; D002986:Clinical Trials as Topic; D003300:Copper / Q000097:blood; D000073840:Copper-Transporting ATPases; D042241:Early Diagnosis; D006527:Hepatolenticular Degeneration / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008403:Mass Screening / Q000379:methods*; D013058:Mass Spectrometry / Q000379:methods; D015997:Neonatal Screening / Q000379:methods; D010446:Peptide Fragments / Q000097:blood
chemical_list: D015415:Biomarkers; D027682:Cation Transport Proteins; D010446:Peptide Fragments; D003300:Copper; D002570:Ceruloplasmin; D000251:Adenosine Triphosphatases; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases
keywords: ATP7B; LC-MRM-MS; LC-MS/MS; Wilson's disease; ceruloplasmin; newborn screening; population screening