Retrospective determination of ceruloplasmin in newborn screening blood spots of patients with Wilson disease

• Published in: Molecular genetics and metabolism 2006-09, Vol.89 (1), p.134-138
• Main Authors: Kroll, Charles A., Ferber, Matt J., Dawson, Brian D., Jacobson, Robert M., Mensink, Kara A., Lorey, Fred, Sherwin, John, Cunningham, George, Rinaldo, Piero, Matern, Dietrich, Hahn, Si Houn
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphatases - genetics; Adolescent; Cation Transport Proteins - genetics; Ceruloplasmin; Ceruloplasmin - analysis; Child; Child, Preschool; Copper-transporting ATPases; Dried blood spots; ELISA; Female; Hepatolenticular Degeneration - diagnosis; Hepatolenticular Degeneration - genetics; Humans; Infant; Male; Mass Screening - methods; Newborn screening; Pediatric screening; Retrospective Studies; Wilson disease
• ISSN: 1096-7192; 1096-7206
• DOI: 10.1016/j.ymgme.2006.03.008

Wilson disease is an autosomal recessive disorder of copper transport, caused by the reduced or absent function of the Wilson disease gene ATP7B on chromosome 13. The disease is characterized by reduced incorporation of copper into the ceruloplasmin protein and reduced excretion of copper into the bile. Wilson disease is effectively treated if detected early. Our study goals were to determine the feasibility of a population screening for Wilson disease using dried blood spots and to characterize the base-line ceruloplasmin concentration in newborn blood spots of patients with Wilson disease. Ceruloplasmin was analyzed in dried blood spots obtained from 353 Mayo Clinic pediatric volunteers aged from 3 months to 18 years and from 1045 anonymous newborn screening specimens using a sandwich enzyme-linked immunosorbent assay. The original newborn screening blood spots were retrieved from two patients with Wilson disease along with age-matched controls for ceruloplasmin determination. The mean (±SD) concentration of ceruloplasmin in the pediatric blood spots was 40.0 ± 14.4 mg/dL (range 13.1 to >60 mg/dL) and newborn blood spots was 47.2 ± 15.5 mg/dL (range 6.5 to >60 mg/dL). Ceruloplasmin in the newborn blood spots from two Wilson disease patients were 2.6 and 2.8 mg/dL, respectively. The newborns affected with Wilson disease had significantly lower ceruloplasmin levels in blood spots than unaffected newborns. These findings support that presymptomatic screening for Wilson disease using dried blood spots could be possible, even in the newborn period.