Wilson Disease: A Pilot Study of Newborn Screening. S. Zafari, C.A. Kroll, J.E. Brown, M.A. Pogatschnik, S.J. Minnich, M.J. Kurke, M.J Ferber, S.H. Hahn. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.
   Background: Wilson disease (WD) is an autosomal recessive disorder of copper transport with an estimated incidence of 1 in 30,000. The disease is progressive and ultimately fatal if untreated. WD is treatable, and serious symptoms can be avoided if an early diagnosis is made. We recently reported that the newborns (NB) affected with WD had significantly lower ceruloplasmin (CP) levels in blood spots than unaffected newborns. Method: We investigated the feasibility of newborn screening for WD using the sandwich ELISA method to support a presymptomatic NB screening for WD. The concentration of CP was measured in the dried blood spots from 6862 blinded NB samples following routine MSMS NB screening with IRB approval. The blood spot samples with CP concentrations lower than 5.0 mg/dL were followed by ATP7b gene mutation analysis to establish an appropriate cut off. Result: The mean CP value was 46.9 20.7 mg/dL (range: 0.1 to >60). Birth weight (BW) ranged from 200g to 5653g and gestational weeks (GW) from 23 to 43. In NB with BW >1800g, the mean CP was 48.3 20.2 mg/dL for those >37 weeks and 33.8 20.0 mg/dL for those <37 weeks. Of these two groups, 0.35% had CP <5.0 mg/dL. In premature NB with BW <1800g (n=124), CP ranged from 0.1 mg/dL to 84.6 mg/dL with a mean of 30.5 23.4 mg/dL. Sixteen of them (12.9%) had CP <5.0 mg/dL, however, we observed an increase in CP in 9 of the 11 premature NB with additional tests over a period of 1 month. In one newborn with a CP of 4.9 mg/dL (BW=3030g), one copy of H1207R alteration was found in the ATP7b gene suggestive of a carrier. No patients were detected in 10 samples sequenced so far and others are yet to be analyzed. Conclusion: 93.8% of NB already reached their CP value >15mg/dL at birth. The repeated tests can significantly reduce false positive rates in premature newborns and will help avoid any unnecessary anxieties to their families and costs for confirmatory tests. Although a pilot study with larger sample number over a longer period is necessary to determine the efficiency of this method, our findings strongly support that presymptomatic newborn screening for WD is feasible.