Falsely elevated C4‐carnitine as expression of glutamate formiminotransferase deficiency in tandem mass spectrometry newborn screening

Malvagia, Sabrina; Marca, Giancarlo la; Casetta, Bruno; Gasperini, Serena; Pasquini, Elisabetta; Zammarchi, Enrico

doi:10.1002/jms.964

Cited by 28 publications

(20 citation statements)

References 14 publications

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“…Formiminoglutamic aciduria, which may appear as a false C 4 alteration (Malvagia et al 2006) is no longer subject to recall because it is considered a benign condition.…”

Section: Standardsmentioning

confidence: 98%

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Progress in expanded newborn screening for metabolic conditions by LC‐MS/MS in Tuscany: Update on methods to reduce false tests

Marca

Malvagia

Casetta³

et al. 2008

J of Inher Metab Disea

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We report on our 6-year experience of expanded newborn screening by tandem mass spectrometry in Tuscany (Italy), the first Italian Region to screen all newborns for more than 40 inborn errors of metabolism: organization, diseases observed and updates on methods to reduce false-positive and false-negative tests are described. Blood collection is recommended between 48 and 72 h of life. Blood spots are sent daily by courier to laboratory. When a positive result occurs, two subsequent procedures are followed: for disorders with possible acute metabolic decompensation, the baby is immediately recalled and clinical examinations and confirmatory tests are performed; for the other disorders, the nursery provides for a second blood spot. If the test is positive, clinical examinations and confirmatory tests are performed. In both cases, if confirmatory tests are positive, a treatment and a follow-up programme are started. Up to now, spots from 160 000 infants have been analysed and 80 affected patients have been identified (disorders of amino acids, organic acids and fatty acids metabolism). We describe adjustments to cut-off values, the introduction of a second-tier test for propionic acidaemia and for methylmalonic aciduria, the inclusion of succinylacetone in the panel of metabolites, and protocols for premature infants and for newborns on parenteral nutrition or transfused. These changes resulted in a reduction in recalls from 1.37% to 0.32% and consequently of working time and parental stress. Avoiding false-negatives by using more specific markers and minimizing the false-positive rate with second-tier testing is important for a successful newborn screening programme.

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“…Formiminoglutamic aciduria, which may appear as a false C 4 alteration (Malvagia et al 2006) is no longer subject to recall because it is considered a benign condition.…”

Section: Standardsmentioning

confidence: 98%

“…Officially mandated by a legislative action, the programme has screened all babies born in Tuscany since November 2004 (approximately 35 000/year) for selected acylcarnitines and amino acids (la Marca et al 2003(la Marca et al , 2005a(la Marca et al , b, 2007Malvagia et al 2006).…”

Section: Introductionmentioning

confidence: 99%

Progress in expanded newborn screening for metabolic conditions by LC‐MS/MS in Tuscany: Update on methods to reduce false tests

Marca

Malvagia

Casetta³

et al. 2008

J of Inher Metab Disea

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“…Second, MS/MS is not sufficiently selective in some cases. Falsepositive test results due to the presence of isobaric contaminants have been reported (13,14 ). Third, acylcarnitine constitutional isomers cannot be distinguished.…”

mentioning

confidence: 99%

Quantification of Carnitine and Acylcarnitines in Biological Matrices by HPLC Electrospray Ionization– Mass Spectrometry

Minkler¹,

Stoll²,

Ingalls³

et al. 2008

Clinical Chemistry

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“…Some diseases identifiable by expanded newborn screening have been included in the panel as conditions that are part of the differential diagnosis of a primary panel condition, such as IBD defect versus SCAD deficiency. Formiminoglutamic aciduria, which may appear as a false butyrrylcarnitine (C4) alteration [39] by using derivatized sample preparation procedures, is no longer subject to recall because it is considered a benign condition. Some authors have considered retaining 3-methyl-crotonylglycinuria in the screening panel, despite it being considered a biochemical condition rather than a disease [40,41].…”

Section: Diseases Included In the Neonatal Screening Programmentioning

confidence: 99%

Mass spectrometry in clinical chemistry: the case of newborn screening

Marca

2014

Journal of Pharmaceutical and Biomedical Analysis

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Keywords:Newborn screening LC-MS/MS Tandem mass spectrometry Inborn errors of metabolism Clinical chemistry a b s t r a c t Newborn screening (NBS) program is a complex and organized system consisting of family and personnel education, biochemical tests, confirmatory biochemical and genetic tests, diagnosis, therapy, and patient follow up. The program identifies treatable metabolic disorders possibly when asymptomatic by using dried blood spot (DBS). During the last 20 years tandem mass spectrometry (TMS) has become the leading technology in NBS programs demonstrating to be versatile, sensitive and specific. There is consistent evidence of benefits from NBS for many disorders detected by TMS as well as for congenital hypothyroidism, cystic fibrosis, congenital adrenal hyperplasia by immune-enzymatic methods.Real time PCR tests have more recently been proposed for the detection of some severe combined immunodeficiences (SCID) along with the use of TMS for ADA and PNP SCID; a first evaluation of their cost-benefit ratio is still ongoing. Avoiding false negative results by using specific biomarkers and reducing the false positive rate by using second tier tests, is fundamental for a successful NBS program. The fully integration of NBS and diagnostic laboratories with clinical service is crucial to have the best effectiveness in a comprehensive NBS system.

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Falsely elevated C4‐carnitine as expression of glutamate formiminotransferase deficiency in tandem mass spectrometry newborn screening

Cited by 28 publications

References 14 publications

Progress in expanded newborn screening for metabolic conditions by LC‐MS/MS in Tuscany: Update on methods to reduce false tests

Progress in expanded newborn screening for metabolic conditions by LC‐MS/MS in Tuscany: Update on methods to reduce false tests

Quantification of Carnitine and Acylcarnitines in Biological Matrices by HPLC Electrospray Ionization– Mass Spectrometry

Mass spectrometry in clinical chemistry: the case of newborn screening

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