Biomedical subjects

John Sherwin

Publications and source records attributed to John Sherwin.

4 recordsLinked to original sources

PubMed2006

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

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+/-15.5mg/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.

Adenosine Triphosphatases↗

PubMed2006

Pilot programs in newborn screening.

The term "pilot study" has been used over the years to describe the evaluation of the many elements involved in deciding whether a proposed condition should be added to a newborn screening (NBS) panel, and until recently, was unilaterally used to describe the evaluation of the assay to be used before the condition was officially adopted by a state for its newborn screening panel. Since Guthrie's introduction of screening for PKU, each time a new condition was added to the panel, the screening assay itself was validated through a population-based trial, in which the test was performed with de-identified samples to avoid association between the test result and the infant. This is considered by the laboratory as the "pilot phase" of adding a new condition. To advance the science of NBS, especially to accommodate new technologies that may provide new types of information (genetic versus physiological) for each new condition, pilot programs are essential. Involvement of the clinical community serves to improve these evaluations and provides the needed clinical validation of decisions made as a result of it. This paper describes the historical context of pilot programs in population-based NBS that utilize laboratory-based markers as indicators of concern; specifically, three applications that demonstrate different approaches to the use of pilots in adding conditions to a NBS panel are described.

Diffusion of Innovation↗

PubMed2006

California's experience implementing a pilot newborn supplemental screening program using tandem mass spectrometry.

OBJECTIVE: In response to a California legislative mandate, a pilot tandem mass spectrometry (MS/MS) screening program was undertaken by the Genetic Disease Branch of the California Department of Health Services between January 2002 and June 2003. This article outlines the Genetic Disease Branch approach to implementing the MS/MS pilot program and the program evaluation strategies used. METHODS: Through the use of multiple data collection methods, we were able to describe hospital participation patterns, screening test uptake, screening test performance, follow-up services utilization, and provider and family satisfaction with the educational materials and follow-up services provided. RESULTS: During the 18-month pilot program, just more than one half of California's 755,698 newborns were offered MS/MS screening; among this group, 90% of parents chose to have their newborns screened. Fifty-one newborns were identified with MS/MS-detectable disorders, among 461 patients referred for follow-up testing (0.13% of the screened population). One disorder was diagnosed successfully for every 6939 newborns screened and for every 9 infants referred (excluding phenylketonuria). The overall California population prevalence of MS/MS-detectable disorders was 1 case per 6500 infants (excluding phenylketonuria). The positive predictive value for medium-chain acyl-CoA dehydrogenase deficiency was 86.7%, whereas the positive predictive value for short-chain acyl-CoA dehydrogenase deficiency was 21.6%. For a sample from Hawaii, 1 isovaleric aciduria case was detected among 6132 newborns. CONCLUSIONS: Evaluation of the California MS/MS screening pilot program demonstrated that this technology was effective in identifying additional metabolic disorders. The positive predictive value of screening was particularly good for medium-chain acyl-CoA dehydrogenase deficiency. Overall, patient referral rates were very acceptable. The utility of the program was also demonstrated by positive reviews from patients and providers.

California↗

PubMed2004

Identification of novel and rare mutations in California Hispanic and African American cystic fibrosis patients.

In ethnic heterogeneous California, complete genetic information is currently lacking to build solid population-based cystic fibrosis (CF) screening programs because a large proportion of mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR/ABCC7) are still unknown, especially in non-Caucasian patients. A total of 402 [46 African American+356 Hispanic] Hispanic and African American patients from California CF patient registry were included in this study. Patients with at least one unidentified mutant allele were asked to donate blood samples for further analysis, first by Genzyme Genetics for a panel of 87 known mutations, followed by temporal temperature gradient gel electrophoresis (TTGE) scanning of the entire coding exons of CFTR gene. A total of eight novel mutations; one missense mutation, one splice-site mutation and six frame-shift mutations were identified. In addition to the eight novel mutations, 20 [corrected] distinct rare mutations that are not in the current available commercial mutation panels were identified by TTGE. The overall detection rate was raised to 95.7% for African American and 94.5% for Hispanic. The discovery of recurrent rare and novel mutations improves the diagnosis and care of persons with CF and improves our ability to adequately and equitably provide screening and genetic counseling services to non-Caucasians.

Adolescent↗