Screening Newborns for Inborn Errors of Metabolism by Tandem Mass Spectrometry

Wilcken, Bridget; Wiley, Veronica; Hammond, Jeremy; Carpenter, Kevin

doi:10.1056/nejmoa025225

Cited by 591 publications

(456 citation statements)

References 18 publications

Supporting

Mentioning

423

Contrasting

Unclassified

Order By: Relevance

“…Treat or Not NBS detects significantly more patients with MCAD and short-chain acyl-CoA dehydrogenase (SCAD) deficiency than are detected by previous clinical manifestations (Wilcken et al 2003;Gallant et al 2012). Patients with MCAD deficiency can present with acute decompensation followed by a poor outcome, and, therefore, early diagnosis and treatment are important.…”

Section: The Occurrences Of False-negative Cases In Nbsmentioning

confidence: 99%

Fatty Acid Oxidation Disorders in a Chinese Population in Taiwan

et al. 2013

View full text Add to dashboard Cite

show abstract

Section: The Occurrences Of False-negative Cases In Nbsmentioning

confidence: 99%

Fatty Acid Oxidation Disorders in a Chinese Population in Taiwan

et al. 2013

View full text Add to dashboard Cite

show abstract

“…Such blood spots are prepared shortly after birth by spotting a drop of newborn blood onto a filter paper card and allowing the liquid to dry on the card. It is now commonplace in many countries to send dried blood spots to newborn screening laboratories for tandem MS analysis of amino acids and acylcarnitines (see, for example, Chace and Kalas (2005), Wilcken et al (2003)). Quantification of these compounds allows screening for up to about 30 treatable metabolic diseases.…”

Section: Tandem Mass Spectrometry For the Multiplex Analysis Of Lysosmentioning

confidence: 99%

Direct multiplex assay of enzymes in dried blood spots by tandem mass spectrometry for the newborn screening of lysosomal storage disorders

Gelb

Tureček

Scott

et al. 2006

J of Inher Metab Disea

185

140

View full text Add to dashboard Cite

SummaryTandem mass spectrometry is currently used in newborn screening programmes to quantify the level of amino acids and acylcarnitines in dried blood spots for detection of metabolites associated with treatable diseases. We have developed assays for lysosomal enzymes in re-hydrated dried blood spots in which a set of substrates is added and the set of corresponding enzymatic products are quantified using tandem mass spectrometry with the aid of mass-differentiated internal standards. We have developed a multiplex assay of the set of enzymes that, when deficient, cause the lysosomal storage disorders Fabry, Gaucher, Hurler, Krabbe, Niemann-Pick A/B and Pompe diseases. These diseases were selected because treatments are now available or expected to emerge shortly. The discovery that acarbose is a selective inhibitor of maltase glucoamylase allows the Pompe disease enzyme, acid α-glucosidase, to be selectively assayed in white blood cells and dried blood spots. When tested with dried blood spots from 40 unaffected individuals and 10-12 individuals with the lysosomal storage disorder, the tandem mass spectrometry assay led to the correct identification of the affected individuals with 100% sensitivity. Many of the reagents needed for the new assays are commercially available, and those that are not are being prepared under Good Manufacturing Procedures for approval by the FDA. Our newborn screening assay for Krabbe disease is currently being put in place at the Wadsworth Center in New York State for the analysis of ~1000 dried blood spots per day.Summary We have developed tandem mass spectrometry for the direct assay of lysosomal enzymes in rehydrated dried blood spots that can be implemented for newborn screening of lysosomal storage disorders. Several enzymes can be analysed by a single method (multiplex analysis) and in a highthroughput manner appropriate for newborn screening laboratories.

show abstract

“…Although most of the fatty acid oxidation disorders affect heart and skeletal muscles and liver, cardiac failure is seen as the major presenting manifestation only in carnitine transporter deficiency (Stanley et al 2006). The disease frequency is ranging from 1:40,000 to 1:120,000 newborns in different parts of the world and is possibly the second most frequent disorder of fatty oxidation after medium chain acyl CoA dehydrogenase deficiency (Koizumi et al 1999;Wilcken et al 2001Wilcken et al , 2003. Studies in cultured fibroblasts from affected patients established that the primary defect in SCD involves the sodium-dependent high-affinity transporter situated in the plasmalemmal membrane (Tein et al 1996;Treem et al 1988).…”

mentioning

confidence: 99%

Identification of Mutations and Evaluation of Cardiomyopathy in Turkish Patients with Primary Carnitine Deficiency

et al. 2011

View full text Add to dashboard Cite

Primary systemic carnitine deficiency (SCD) is an autosomal recessive disorder caused by defective cellular carnitine transport. Patients usually present with predominant metabolic or cardiac manifestations. SCD is caused by mutations in the organic cation/carnitine transporter OCTN2 (SLC22A5) gene. Mutation analysis of SLC22A5 gene was carried out in eight Turkish patients from six families. Six patients presented with signs and symptoms of heart failure, cardiomyopathy, and low plasma carnitine levels, five of them with concurrent anemia. A patient with dilated cardiomyopathy had also facial dysmorphia, microcephaly, and developmental delay. Tandem MS analyses in siblings of the patients revealed two more cases with low plasma carnitine levels. SCD diagnosis was confirmed in these two cases by mutation screening. These two cases were asymptomatic but echocardiography revealed left ventricular dilatation in one of them. Carnitine treatment was started before the systemic signs and symptoms developed in these patients. Mean value of serum carnitine levels of the patients was 2.63 AE 1.92 mmol/L at the time of diagnosis. After 1 year of treatment, carnitine values increased to 16.62 AE 5.11 (p < 0.001) and all responded to carnitine supplementation clinically.

show abstract

Screening Newborns for Inborn Errors of Metabolism by Tandem Mass Spectrometry

Abstract: More cases of inborn errors of metabolism are diagnosed by screening with tandem mass spectrometry than are diagnosed clinically. It is not yet clear which patients with disorders diagnosed by such screening would have become symptomatic if screening had not been performed.

Cited by 591 publications

References 18 publications

Fatty Acid Oxidation Disorders in a Chinese Population in Taiwan

Fatty Acid Oxidation Disorders in a Chinese Population in Taiwan

Direct multiplex assay of enzymes in dried blood spots by tandem mass spectrometry for the newborn screening of lysosomal storage disorders

Identification of Mutations and Evaluation of Cardiomyopathy in Turkish Patients with Primary Carnitine Deficiency

Contact Info

Product

Resources

About