Application of a Second-Tier Newborn Screening Assay for C5 Isoforms

Cloppenborg, Thomas; Janzen, Nils; Hj, Wagner; Steuerwald, Ulrike; Peter, Michael; Das, AM

doi:10.1007/8904_2013_275

Cited by 9 publications

(8 citation statements)

References 14 publications

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“…The maximum C5-acylcarnitine blood concentration was reached 4 hours after balm ingestion in all volunteers. Considering that the pivalic acid derivative neopentanoic acid conjugates the free carnitine [4][5][6] and that the breast-feeding period could be quite long (generally some months), we cannot exclude a potentially dangerous secondary carnitine deficiency due to a long-term nipple fissure balm application. Exogenous unusual long-term pivalate exposure from pivalic esters of antibiotics to mothers or newborns had previously been reported as responsible for carnitine depletion and hypoglycemic convulsions.…”

Section: Resultsmentioning

confidence: 99%

“…Moreover, an increase in C5-acylcarnitine due to the presence of pivaloylcarnitine (PC) originating from pivalic acid in some antibiotic preparations and generating many falsepositive results in newborn screening programs has been reported in the literature. 4,5 More recently, Boemer and collaborators described a pivalic acid derivative ''neopentanoate'' used in the cosmetic industry to formulate a nipple fissure unguent that leads to false-positive increases in C5-acylcarnitine. 6 In 2015, Yamada and colleagues reported on 2 cases that developed elevated C5-acylcarnitine levels following treatment with sivelestat, a neutrophil elastase inhibitor used to treat acute respiratory distress syndrome.…”

Section: Introductionmentioning

confidence: 99%

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Reducing the False-Positive Rate for Isovalerylcarnitine in Expanded Newborn Screening

Poggiali

Ombrone

Forni

et al. 2016

Journal of Inborn Errors of Metabolism and Screening

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The isodecyl neopentanoate is an ingredient used in the cosmetic industry to prepare a nipple fissure balm. We report on 12 newborns that showed elevated C5-acylcarnitine levels upon newborn screening following treatment with balm. The first 3 neonates were immediately recalled for confirmatory tests and resulted negative for both isovaleric acidemia and short/branched chain acyl-CoA dehydrogenase deficiency. In the other 9 cases, the immediate recall was avoided by applying a new second-tier test able to confirm the presence of pivaloylcarnitine. The concentration of C5-acylcarnitine was measured in the days following the suspension of balm application. Abnormal concentrations of C5-acylcarnitine did not seem to be associated with free carnitine deficiency, probably due to the short time of exposure. A direct correlation between balm ingestion and the elevation in pivaloylcarnitine has been demonstrated in 10 adult volunteers. The commercial balm containing a pivalic acid derivative is causal of false-positive results during newborn screening, and it could have the potential to cause secondary carnitine deficiency when used chronically.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Reducing the False-Positive Rate for Isovalerylcarnitine in Expanded Newborn Screening

Poggiali

Ombrone

Forni

et al. 2016

Journal of Inborn Errors of Metabolism and Screening

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“…In order to differentiate SBCADD from IVA and to exclude interference from antibiotics, urine acylglycine analysis and/or quantitative organic acid analysis are performed. Furthermore, several strategies for second-tier testing in dried blood spots have been developed, including stable isotope dilution MS/MS analysis to determine isovalerylglycine [63,64] and ultra-performance liquid chromatography (UPLC)-MS/MS analysis of C5-carnitines [59,65].…”

Section: Iva Newborn Screening: Diagnosis Birth Prevalence and Diffementioning

confidence: 99%

“…With NBS becoming an important part of pediatric preventive strategies worldwide, several diagnostic pitfalls have come to attention. Pivaloylcarnitine, a derivative of antibiotics containing pivalic acid, can be mistaken for isovalerylcarnitine in NBS blood samples, and treatment of mothers with these antibiotics before delivery has been blamed for a number of false positive NBS results [ 57 , 58 , 59 , 60 , 61 ]. Sivelestat, a neutrophil elastase inhibitor used to treat acute respiratory distress syndrome, also contains pivalic acid and can lead to false positive NBS results for IVA [ 62 ].…”

Section: Iva Newborn Screening: Diagnosis Birth Prevalence and DImentioning

confidence: 99%

Aspects of Newborn Screening in Isovaleric Acidemia

Schlune

Riederer

Mayatepek

et al. 2018

IJNS

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Isovaleric acidemia (IVA), an inborn error of leucine catabolism, is caused by mutations in the isovaleryl-CoA dehydrogenase (IVD) gene, resulting in the accumulation of derivatives of isovaleryl-CoA including isovaleryl (C5)-carnitine, the marker metabolite used for newborn screening (NBS). The inclusion of IVA in NBS programs in many countries has broadened knowledge of the variability of the condition, whereas prior to NBS, two distinct clinical phenotypes were known, an "acute neonatal" and a "chronic intermittent" form. An additional biochemically mild and potentially asymptomatic form of IVA and its association with a common missense mutation, c.932C>T (p.A282V), was discovered in subjects identified through NBS. Deficiency of short/branched chain specific acyl-CoA dehydrogenase (2-methylbutyryl-CoA dehydrogenase), a defect of isoleucine degradation whose clinical significance remains unclear, also results in elevated C5-carnitine, and may therefore be detected by NBS for IVA. Treatment strategies for the long-term management of symptomatic IVA comprise the prevention of catabolism, dietary restriction of natural protein or leucine intake, and supplementation with L-carnitine and/or L-glycine. Recommendations on how to counsel and manage individuals with the mild phenotype detected by NBS are required.

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“…For this reason, to date, an increasing number of publications relate to the development of second-tier test is reported [52][53][54][55][56]. …”

Section: Second Tier Testsmentioning

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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Application of a Second-Tier Newborn Screening Assay for C5 Isoforms

Cited by 9 publications

References 14 publications

Reducing the False-Positive Rate for Isovalerylcarnitine in Expanded Newborn Screening

Reducing the False-Positive Rate for Isovalerylcarnitine in Expanded Newborn Screening

Aspects of Newborn Screening in Isovaleric Acidemia

Mass spectrometry in clinical chemistry: the case of newborn screening

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