Missed Newborn Screening Case of Carnitine Palmitoyltransferase-II Deficiency

Edmondson, Andrew C.; Salant, Jennifer A.; Ierardi-Curto, Lynne; Fıçıcıoğlu, Can

doi:10.1007/8904_2016_528

Cited by 20 publications

(13 citation statements)

References 19 publications

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“…The occurrence of false-negative cases is expected in any screening program [ 19 , 52 ]. It is well known that myopathic CPT-II [ 54 , 55 ] and variant MSUD [ 52 , 56 ] may be missed due to screening markers lying below the action limit. In Norway, the incidence of intermittent MSUD is more common than that of the classical phenotype [ 57 ], and it is likely that most intermittent MSUD cases will be missed using the existing screening algorithm.…”

Section: Discussionmentioning

confidence: 99%

Performance of Expanded Newborn Screening in Norway Supported by Post-Analytical Bioinformatics Tools and Rapid Second-Tier DNA Analyses

Tangeraas

Sæves

Klingenberg

et al. 2020

IJNS

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In 2012, the Norwegian newborn screening program (NBS) was expanded (eNBS) from screening for two diseases to that for 23 diseases (20 inborn errors of metabolism, IEMs) and again in 2018, to include a total of 25 conditions (21 IEMs). Between 1 March 2012 and 29 February 2020, 461,369 newborns were screened for 20 IEMs in addition to phenylketonuria (PKU). Excluding PKU, there were 75 true-positive (TP) (1:6151) and 107 (1:4311) false-positive IEM cases. Twenty-one percent of the TP cases were symptomatic at the time of the NBS results, but in two-thirds, the screening result directed the exact diagnosis. Eighty-two percent of the TP cases had good health outcomes, evaluated in 2020. The yearly positive predictive value was increased from 26% to 54% by the use of the Region 4 Stork post-analytical interpretive tool (R4S)/Collaborative Laboratory Integrated Reports 2.0 (CLIR), second-tier biochemical testing and genetic confirmation using DNA extracted from the original dried blood spots. The incidence of IEMs increased by 46% after eNBS was introduced, predominantly due to the finding of attenuated phenotypes. The next step is defining which newborns would truly benefit from screening at the milder end of the disease spectrum. This will require coordinated international collaboration, including proper case definitions and outcome studies.

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Section: Discussionmentioning

confidence: 99%

Performance of Expanded Newborn Screening in Norway Supported by Post-Analytical Bioinformatics Tools and Rapid Second-Tier DNA Analyses

Tangeraas

Sæves

Klingenberg

et al. 2020

IJNS

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“…Further, medical investigation to rule out the disease consumes resources of time and money [ 17 ]. FAODs are sometimes difficult to diagnose due to decreased acylcarnitine levels in anabolic conditions [ [18] , [19] , [20] ]. Patients with MCAD deficiency tend to have elevated C8, C10, and C8/C10 ratios throughout their life [ 21 ], whereas C8 and C10 levels could decrease in a time-series, especially in equivocal cases [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

Essential oils can cause false-positive results of medium-chain acyl-CoA dehydrogenase deficiency

Mikami-Saito

Maekawa

Wada

et al. 2020

Molecular Genetics and Metabolism Reports

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Newborn screening is a public health care program worldwide to prevent patients from critical illness or conditions. Tandem mass spectrometry allows multiplex, inexpensive, and rapid newborn screening. However, mass spectrometry used for newborn screening to date is not able to separate peaks of compounds with similar m/z , which could lead to false-positive results without additional second-tier tests, such as fragmentation. We experienced three neonatal cases with high levels of markers, octanoylcarnitine and octanoylcarnitine/decanoylcarnitine ratio used to pick up possible cases of medium-chain acyl-CoA dehydrogenase (MCAD) deficiency. The babies were born consecutively in a maternity hospital. Their second acylcarnitine profiles were normal, and the genetic tests for ACADM were negative. Analysis of samples extracted from their first Guthrie cards where blood was not stained also showed peaks equivalent to octanoylcarnitine and decanoylcarnitine, indicating contamination. Environmental surveillance in the maternity ward suggested that essential oils used there might contain the contaminated compound. LC-HRMS/MS and in silico analysis revealed that false-positive results might be due to contamination with the essential oils in Guthrie cards, and causal agents were sphinganine (d17:0) and 2-[2-hydroxyethyl(pentadecyl)amino]ethanol. Thus, health care providers should be cautioned about use of essential oils when collecting blood samples on Guthrie cards. False-positive results can waste costly social resources and cause a physical and psychological burden for children and parents.

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“…It has become increasingly apparent that the classical forms of IEM, with presentation in infancy or childhood, are just the tip of the iceberg. Milder variants that may not cause clinical symptoms until adulthood or in states of increased metabolic stress (pregnancy, infections, surgery, ketogenic diet), resulting in a pool of patients likely to be missed by NBS (52,53). Inherited metabolic diseases may often be overlooked in the differential diagnosis for older patients or children who had a normal newborn screen, but case reports suggest that atypical presentations may be relatively common in this patient population (54).…”

Section: Discussionmentioning

confidence: 99%

Laboratory diagnostic approaches in metabolic disorders

Guerrero¹,

Salazar²,

Tanpaiboon³

2018

Ann. Transl. Med

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The diagnosis of inborn errors of metabolism (IEM) takes many forms. Due to the implementation and advances in newborn screening (NBS), the diagnosis of many IEM has become relatively easy utilizing laboratory biomarkers. For the majority of IEM, early diagnosis prevents the onset of severe clinical symptoms, thus reducing morbidity and mortality. However, due to molecular, biochemical, and clinical variability of IEM, not all disorders included in NBS programs will be detected and diagnosed by screening alone. This article provides a general overview and simplified guidelines for the diagnosis of IEM in patients with and without an acute metabolic decompensation, with early or late onset of clinical symptoms. The proper use of routine laboratory results in the initial patient assessment is also discussed, which can help guide efficient ordering of specialized laboratory tests to confirm a potential diagnosis and initiate treatment as soon as possible.

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Missed Newborn Screening Case of Carnitine Palmitoyltransferase-II Deficiency

Cited by 20 publications

References 19 publications

Performance of Expanded Newborn Screening in Norway Supported by Post-Analytical Bioinformatics Tools and Rapid Second-Tier DNA Analyses

Performance of Expanded Newborn Screening in Norway Supported by Post-Analytical Bioinformatics Tools and Rapid Second-Tier DNA Analyses

Essential oils can cause false-positive results of medium-chain acyl-CoA dehydrogenase deficiency

Laboratory diagnostic approaches in metabolic disorders

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