Newborn screening with tandem mass spectrometry: 12 months' experience in NSW Australia

Wiley, Veronica

doi:10.1080/080352599750029376

Cited by 31 publications

(34 citation statements)

References 6 publications

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“…Recently, however, there has been much confusion about which disorders are detectable by MS/MS and how it should be used in their detection. The number of diseases detectable by MS/MS, as reported in the literature, generally numbers around 20, with ranges from 10 to Ͼ40 (16,17,72,78 ). Our discussion here concerns primarily newborns, although much of the literature describes children whose disorders were detected at an older age when they became unwell.…”

Section: Disorders Of Amino Acid Fatty Acid and Organic Acid Metabomentioning

confidence: 95%

Use of Tandem Mass Spectrometry for Multianalyte Screening of Dried Blood Specimens from Newborns

Chace¹,

Kalas²,

Naylor³

2003

Clinical Chemistry

566

366

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Background: Over the past decade laboratories that test for metabolic disorders have introduced tandem mass spectrometry (MS/MS), which is more sensitive, specific, reliable, and comprehensive than traditional assays, into their newborn-screening programs. MS/MS is rapidly replacing these one-analysis, one-metabolite, one-disease classic screening techniques with a oneanalysis, many-metabolites, many-diseases approach that also facilitates the ability to add new disorders to existing newborn-screening panels. Methods: During the past few years experts have authored many valuable articles describing various approaches to newborn metabolic screening by MS/MS. We attempted to document key developments in the introduction and validation of MS/MS screening for metabolic disorders. Our approach used the perspective of the metabolite and which diseases may be present from its detection rather than a more traditional approach of describing a disease and noting which metabolites are increased when it is present. Content: This review cites important historical developments in the introduction and validation of MS/MS screening for metabolic disorders. It also offers a basic technical understanding of MS/MS as it is applied to multianalyte metabolic screening and explains why MS/MS is well suited for analysis of amino acids and acylcarnitines in dried filter-paper blood specimens. It also describes amino acids and acylcarnitines as they are detected and measured by MS/MS and their significance to the identification of specific amino acid, fatty acid, and organic acid disorders. Conclusions: Multianalyte technologies such as MS/MS are suitable for newborn screening and other mass

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Section: Disorders Of Amino Acid Fatty Acid and Organic Acid Metabomentioning

confidence: 95%

Use of Tandem Mass Spectrometry for Multianalyte Screening of Dried Blood Specimens from Newborns

Chace¹,

Kalas²,

Naylor³

2003

Clinical Chemistry

566

366

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“…Within the United States, the New England consortium seems to provide an excellent working model, which addresses important aspects of management (Albers et al, 2001a;Gempel et al, 2002). The method is highly sensitive and specific (Wiley et al, 1999). Although perinatal CPT II deficiency is almost invariably fatal, early diagnosis is still useful.…”

Section: Diagnosismentioning

confidence: 99%

Carnitine Palmitoyltransferase II Deficiency: A Clinical, Biochemical, and Molecular Review

Sigauke

Rakheja

Kitson

et al. 2003

Laboratory Investigation

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SUMMARY:Congenital deficiency of carnitine palmitoyltransferase (CPT) II has been known for at least 30 years now, and its phenotypic variability remains fascinating. Three distinct clinical entities have been described, the adult, the infantile, and the perinatal, all with an autosomal recessive inheritance pattern. The adult CPT II clinical phenotype is somewhat benign and requires additional external triggers such as high-intensity exercise before the predominantly myopathic symptoms are elicited. The perinatal and infantile forms involve multiple organ systems. The perinatal disease is the most severe form and is invariably fatal. The introduction of mass spectrometry to analyze blood acylcarnitine profiles has revolutionized the diagnosis of fatty acid oxidation disorders including CPT II deficiency. Its use in expanded neonatal screening programs has made presymptomatic diagnosis a reality. An increasing number of mutations are being identified in the CPT II gene with a distinct genotype-phenotype correlation in most cases. However, clinical variability in some patients suggests additional genetic or environmental modifiers. Herein, we present a new case of lethal perinatal CPT II deficiency with a rare missense mutation, R296Q (907GϾA) associated with a previously described 25-bp deletion on the second allele. We review the clinical features, the diagnostic protocol including expanded neonatal screening, the treatment, and the biochemical and molecular basis of CPT II deficiency. (Lab Invest 2003, 83:1543-1554.T he carnitine palmitoyltransferase (CPT) enzyme system, in association with acyl-coenzyme A (CoA) synthetase and the carnitine-acylcarnitine translocase (CACT), plays an important role in the transfer of long chain fatty acids (LCFA) from the cytosolic compartment to the mitochondrial matrix, where ␤-oxidation occurs (Bieber, 1988). Two genetically distinct mitochondrial membrane-bound enzymes make up the CPT system. CPT I is located on the inner aspect of the outer mitochondrial membrane. This enzyme is physiologically inhibited by the high levels of malonyl-CoA that occur postprandially and thus regulates the entry of LCFA into the mitochondria (McGarry and Brown, 1997). CPT II, which is not inhibited by malonyl-CoA, is situated on the inner aspect of the inner mitochondrial membrane (Murthy and Pande, 1987).CPT II deficiency was first reported by DiMauro and DiMauro (1973) in adults with exercise-induced rhabdomyolysis. It is an autosomal recessive disorder (Angelini et al, 1981;Meola et al, 1987) and is now regarded as one of the most common inherited disorders of lipid metabolism . Isolated presentation in two successive generations has been reported, indicating a possible dominant inheritance (Mongini et al, 1991). Partial CPT II deficiency with an autosomal dominant inheritance pattern has also been reported (Ionasescu et al, 1980). The molecular basis for this presentation was not elucidated.To date, three distinct CPT II-deficient phenotypes have been described in the literature, for wh...

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“…The boy was born at term, the first child of first cousin parents of Lebanese extraction. A routine newborn screening sample taken on day 3 [Wiley et al, 1999] showed an increase in C5-hydroxyacylcarnitine, 2.5 mmol/L (the cut off value for further investigation in the screening program was 1.5 mmol/L, representing approximately the 99.95th percentile). A urine sample on day 15 had grossly increased 3-methylglutaconate but no increase in 3-hydroxyisovalerate, 3-methylglutarate, or 3-hydroxy-3-methylglutarate, and 2-ethylhydracrylate (2-ethyl-3-hydroxypropionate) was detected.…”

Section: Patients and Methods Patientsmentioning

confidence: 99%

Mutations in theAUH gene cause 3-methylglutaconic aciduria type I

Peters

Gibson

et al. 2003

Hum. Mutat.

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Newborn screening with tandem mass spectrometry: 12 months' experience in NSW Australia

Cited by 31 publications

References 6 publications

Use of Tandem Mass Spectrometry for Multianalyte Screening of Dried Blood Specimens from Newborns

Use of Tandem Mass Spectrometry for Multianalyte Screening of Dried Blood Specimens from Newborns

Carnitine Palmitoyltransferase II Deficiency: A Clinical, Biochemical, and Molecular Review

Mutations in theAUH gene cause 3-methylglutaconic aciduria type I

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