The tandem mass spectrometry newborn screening experience in North Carolina: 1997–2005

Abstract

North Carolina (NC) was the first US state to initiate universal tandem mass spectrometry (MS/MS) newborn screening. This began as a statewide pilot project in 1997 to determine the incidence and feasibility of screening for fatty acid oxidation, organic acid and selected amino acid disorders. The MS/MS analyses were done by a commercial laboratory and all follow-up and confirmatory testing was performed through the NC Newborn Screening (NBS) Program. In April 1999, the NC NBS Laboratory began the MS/MS analyses in-house. Between 28 July 1997 and 28 July 2005, 944,078 infants were screened and 219 diagnoses were confirmed on newborns with elevated screening results, for an overall incidence of 1:4,300. Ninety-nine infants were identified with fatty acid oxidation disorders, 58 with organic acidaemias and 62 with aminoacidopathies. Medium-chain acyl-CoA dehydrogenase deficiency, 3-methylcrotonyl-CoA carboxylase deficiency and disorders of phenylalanine metabolism were the most common disorders detected. Identification of affected infants has allowed retrospective testing of other family members, resulting in an additional 16 diagnoses. Seven neonates died from complications of their metabolic disorders/prematurity despite timely MS/MS screening. In addition, there were six infants who were not identified by elevated NBS results but who presented with symptoms later in infancy. The NC MS/MS NBS Program uses a two-tier system, categorizing results as either 'borderline' or 'diagnostic' elevated, for both the cutoffs and follow-up protocol. Infants with an initial borderline result had only a repeat screen. Infants with a diagnostic or two borderline results were referred for confirmatory testing. The positive predictive value of the NC MS/MS NBS for those infants requiring confirmatory testing was 53% for 2003 and 2004. The success of the NC MS/MS NBS Program in identifying infants with metabolic disorders was dependent on a comprehensive follow-up protocol integrating the public health laboratory and the academic metabolic centres.

Organic Acidurias: An Updated Review

“…There are also other studies which report a higher prevalence of OAD in India (Please see details mentioned below). OADs were seen in some Western countries, for example in North Carolina, as reported by Frazier et al [17].…”

Selective Screening for Inborn Errors of Metabolism: A Report of Six Years Experience

“…The use of Tandem Mass Spectrometry (MS) is widely growing for implementation of newborn screening (NBS) programs for IEM as well as for selective screening of children at various ages. The results obtained from these expanded NBS programs have provided information about the prevalence of these disorders in the population in USA and also in some European countries (2)(3)(4)(5)(6)(7)(8).…”

Birth Prevalence of Fatty Acid β-Oxidation Disorders in Iberia

“…Since the introduction of FAOD in the screening panels of NBS programs, generated data has pointed to a significant increase in the disease incidence (Wilcken et al 2007) that is now believed to be about 1:9,000, although some significant differences can be observed between different populations (Zytkovicz et al 2001;Wilcken et al 2003;Frazier et al 2006;Kasper et al 2010;Lindner et al 2011;Lund et al 2012). In the pre-NBS era, diagnosis was achieved mainly through organic acid analysis in the urine of symptomatic patients that resulted in a low detection rate, which together with the detection of potentially asymptomatic patients through NBS, justifies the observed difference (Sturm et al 2012).…”