A False-Positive Case of Methylmalonic Aciduria by Tandem Mass Spectrometry Newborn Screening Dependent on Maternal Malnutrition in Pregnancy

Claudia Rossi, Ilaria Cicalini, Cristiano Rizzo, Mirco Zucchelli, Ada Consalvo, Silvia Valentinuzzi, Daniela Semeraro, Giorgia Gasparroni, Patrizia Brindisino, Diego Gazzolo, Carlo Dionisi-Vici, Vincenzo De Laurenzi and Damiana Pieragostino
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Claudia Rossi: Center for Advanced Studies and Technology (CAST), University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy
Ilaria Cicalini: Center for Advanced Studies and Technology (CAST), University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy
Cristiano Rizzo: Metabolic Diseases Unit, Bambino Gesù Children Hospital and Research Institute, 00165 Rome, Italy
Mirco Zucchelli: Center for Advanced Studies and Technology (CAST), University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy
Ada Consalvo: Center for Advanced Studies and Technology (CAST), University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy
Silvia Valentinuzzi: Center for Advanced Studies and Technology (CAST), University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy
Daniela Semeraro: Center for Advanced Studies and Technology (CAST), University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy
Giorgia Gasparroni: Neonatal Intensive Care Unit, University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy
Patrizia Brindisino: Neonatal Intensive Care Unit, University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy
Diego Gazzolo: Department of Medicine and Aging Science, University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy
Carlo Dionisi-Vici: Metabolic Diseases Unit, Bambino Gesù Children Hospital and Research Institute, 00165 Rome, Italy
Vincenzo De Laurenzi: Center for Advanced Studies and Technology (CAST), University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy
Damiana Pieragostino: Center for Advanced Studies and Technology (CAST), University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy

IJERPH, 2020, vol. 17, issue 10, 1-10

Abstract: Methylmalonic Acidurias (MMAs) are a group of inborn errors of metabolism (IEMs), specifically of propionate catabolism characterized by gastrointestinal and neurometabolic manifestations resulting from a deficiency in the function of methylmalonyl-CoA mutase, methylmalonyl-CoA epimerase, and cobalamin metabolism. In Expanded Newborn Screening (NBS), increased levels of propionylcarnitine (C3) and/or of its ratios by MS/MS analysis of dried blood spots (DBS) samples are suggestive for either Propionic Acidemia or MMAs. C3 elevation is not considered a specific marker for these disorders, resulting in high false-positive rates. The use of analyte ratios improves specificity, but it still cannot resolve the diagnostic issue. Second-tier testing are strongly recommended as confirmation of primary NBS results and for a differential diagnosis. LC-MS/MS analysis allows the quantification of more specific markers of the disorder. Here, we report the case of a newborn with a suspected MMA at Expanded NBS and at second-tier test. Given the urgent situation, in-depth diagnostic investigations were performed. Further investigations surprisingly revealed a Vitamin B12 deficiency due to a maternal malnutrition during pregnancy. This case emphasized that metabolic alterations at NBS may not only be influenced by genome and related to IEMs, but also to external factors and to maternal conditions.

Keywords: organic acidemias; newborn screening; methylmalonic acidemia; false-positive; mass spectrometry; vitamin B12 deficiency; LC-MS/MS; maternal defects (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2020
References: View complete reference list from CitEc
Citations: View citations in EconPapers (2)

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