Efficacy and outcome of expanded newborn screening for metabolic diseases - Report of 10 years from South-West Germany *

Abstract

BackgroundNational newborn screening programmes based on tandem-mass spectrometry (MS/MS) and other newborn screening (NBS) technologies show a substantial variation in number and types of disorders included in the screening panel. Once established, these methods offer the opportunity to extend newborn screening panels without significant investment and cost. However, systematic evaluations of newborn screening programmes are rare, most often only describing parts of the whole process from taking blood samples to long-term evaluation of outcome.MethodsIn a prospective single screening centre observational study 373 cases with confirmed diagnosis of a metabolic disorder from a total cohort of 1,084,195 neonates screened in one newborn screening laboratory between January 1, 1999, and June 30, 2009 and subsequently treated and monitored in five specialised centres for inborn errors of metabolism were examined. Process times for taking screening samples, obtaining results, initiating diagnostic confirmation and starting treatment as well as the outcome variables metabolic decompensations, clinical status, and intellectual development at a mean age of 3.3 years were evaluated.ResultsOptimal outcome is achieved especially for the large subgroup of patients with medium-chain acyl-CoA dehydrogenase deficiency. Kaplan-Meier-analysis revealed disorder related patterns of decompensation. Urea cycle disorders, organic acid disorders, and amino acid disorders show an early high and continuous risk, medium-chain acyl-CoA dehydrogenase deficiency a continuous but much lower risk for decompensation, other fatty acid oxidation disorders an intermediate risk increasing towards the end of the first year. Clinical symptoms seem inevitable in a small subgroup of patients with very early disease onset. Later decompensation can not be completely prevented despite pre-symptomatic start of treatment. Metabolic decompensation does not necessarily result in impairment of intellectual development, but there is a definite association between the two.ConclusionsPhysical and cognitive outcome in patients with presymptomatic diagnosis of metabolic disorders included in the current German screening panel is equally good as in phenylketonuria, used as a gold standard for NBS. Extended NBS entails many different interrelated variables which need to be carefully evaluated and optimized. More reports from different parts of the world are needed to allow a comprehensive assessment of the likely benefits, harms and costs in different populations.

Medium-Chain Acyl-CoA Dehydrogenase Deficiency: Evaluation of Genotype-Phenotype Correlation in Patients Detected by Newborn Screening

“…MCADD is widely accepted as suitable condition for newborn screening, as death or neurological sequelae can mostly be prevented by prophylactic measures (NennstielRatzel et al 2005;Wilcken et al 2007;Lindner et al 2011). This finding could be replicated in our follow-up study.…”

“…Minimal criteria for confirmation of MCADD are a characteristic acylcarnitine profile in dried blood and presence of hexanoylglycine in urine or an informative genotype or reduced enzyme activity. In this study we report follow-up data based on the biochemical and clinical phenotypes of 37 patients with MCADD who took part in a study on long-term outcome of patients with inborn errors of metabolism detected by newborn screening (Lindner et al 2011) and in whom information on genotype (both alleles) was available.…”

“…It is included in many newborn screening programmes worldwide (National Newborn Screening and Genetics Resource Center, Austin, Texas; Bundesausschuss 2005; Wilcken et al 2007). Outcome is predominantly excellent following presymptomatic diagnosis, if prolonged fasting is avoided and adequate emergency management is performed during episodes of metabolic stress (Wilcken et al 2007;Lindner et al 2011). In cohorts diagnosed symptomatically, about 20% of patients died from their first metabolic decompensation, 20% showed severe neurological sequelae (Derks et al 2006).…”

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).…”

Fatty Acid Oxidation Disorders in a Chinese Population in Taiwan

“…Currently, different sets of FAO disorders are screened in different countries. The American College of Clinical Genetics proposed 29 core and 25 secondary conditions for screening, which include most of the FAO disorders (2006), while only 5 FAO disorders are included in screening in Germany (Lindner et al 2011). In Taiwan, MS/MS was introduced in 2001 (Huang et al 2006); however, only MCAD deficiency is recommended by the Bureau of Health Promotion, Department of Health, and all other FAO disorders can be screened only after the parents' consent (Niu et al 2010).…”