PMID- 32443888 OWN - NLM STAT- MEDLINE DCOM- 20201019 LR - 20201019 IS - 1660-4601 (Electronic) IS - 1661-7827 (Print) IS - 1660-4601 (Linking) VI - 17 IP - 10 DP - 2020 May 20 TI - A False-Positive Case of Methylmalonic Aciduria by Tandem Mass Spectrometry Newborn Screening Dependent on Maternal Malnutrition in Pregnancy. LID - 10.3390/ijerph17103601 [doi] LID - 3601 AB - 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. FAU - Rossi, Claudia AU - Rossi C AUID- ORCID: 0000-0003-0949-0280 AD - Center for Advanced Studies and Technology (CAST), University "G. d'Annunzio" of Chieti-Pescara, 66100 Chieti, Italy. AD - Department of Medicine and Aging Science, University "G. d'Annunzio" of Chieti-Pescara, 66100 Chieti, Italy. FAU - Cicalini, Ilaria AU - Cicalini I AUID- ORCID: 0000-0002-9792-2225 AD - Center for Advanced Studies and Technology (CAST), University "G. d'Annunzio" of Chieti-Pescara, 66100 Chieti, Italy. AD - Department of Medicine and Aging Science, University "G. d'Annunzio" of Chieti-Pescara, 66100 Chieti, Italy. FAU - Rizzo, Cristiano AU - Rizzo C AD - Metabolic Diseases Unit, Bambino Gesu Children Hospital and Research Institute, 00165 Rome, Italy. FAU - Zucchelli, Mirco AU - Zucchelli M AD - Center for Advanced Studies and Technology (CAST), University "G. d'Annunzio" of Chieti-Pescara, 66100 Chieti, Italy. AD - Department of Medical, Oral and Biotechnological Sciences, University "G. d'Annunzio" of Chieti-Pescara, 66100 Chieti, Italy. FAU - Consalvo, Ada AU - Consalvo A AD - Center for Advanced Studies and Technology (CAST), University "G. d'Annunzio" of Chieti-Pescara, 66100 Chieti, Italy. AD - Department of Medical, Oral and Biotechnological Sciences, University "G. d'Annunzio" of Chieti-Pescara, 66100 Chieti, Italy. FAU - Valentinuzzi, Silvia AU - Valentinuzzi S AD - Center for Advanced Studies and Technology (CAST), University "G. d'Annunzio" of Chieti-Pescara, 66100 Chieti, Italy. AD - Department of Pharmacy, University "G. d'Annunzio" of Chieti-Pescara, 66100 Chieti, Italy. FAU - Semeraro, Daniela AU - Semeraro D AD - Center for Advanced Studies and Technology (CAST), University "G. d'Annunzio" of Chieti-Pescara, 66100 Chieti, Italy. AD - Department of Medicine and Aging Science, University "G. d'Annunzio" of Chieti-Pescara, 66100 Chieti, Italy. FAU - Gasparroni, Giorgia AU - Gasparroni G AD - Neonatal Intensive Care Unit, University "G. d'Annunzio" of Chieti-Pescara, 66100 Chieti, Italy. FAU - Brindisino, Patrizia AU - Brindisino P AD - Neonatal Intensive Care Unit, University "G. d'Annunzio" of Chieti-Pescara, 66100 Chieti, Italy. FAU - Gazzolo, Diego AU - Gazzolo D AD - Department of Medicine and Aging Science, University "G. d'Annunzio" of Chieti-Pescara, 66100 Chieti, Italy. AD - Neonatal Intensive Care Unit, University "G. d'Annunzio" of Chieti-Pescara, 66100 Chieti, Italy. FAU - Dionisi-Vici, Carlo AU - Dionisi-Vici C AD - Metabolic Diseases Unit, Bambino Gesu Children Hospital and Research Institute, 00165 Rome, Italy. FAU - De Laurenzi, Vincenzo AU - De Laurenzi V AD - Center for Advanced Studies and Technology (CAST), University "G. d'Annunzio" of Chieti-Pescara, 66100 Chieti, Italy. AD - Department of Medical, Oral and Biotechnological Sciences, University "G. d'Annunzio" of Chieti-Pescara, 66100 Chieti, Italy. FAU - Pieragostino, Damiana AU - Pieragostino D AUID- ORCID: 0000-0003-1015-3484 AD - Center for Advanced Studies and Technology (CAST), University "G. d'Annunzio" of Chieti-Pescara, 66100 Chieti, Italy. AD - Department of Medical, Oral and Biotechnological Sciences, University "G. d'Annunzio" of Chieti-Pescara, 66100 Chieti, Italy. LA - eng PT - Case Reports PT - Journal Article DEP - 20200520 PL - Switzerland TA - Int J Environ Res Public Health JT - International journal of environmental research and public health JID - 101238455 RN - 8LL8S712J7 (Methylmalonic Acid) RN - Methylmalonic acidemia SB - IM MH - *Amino Acid Metabolism, Inborn Errors/diagnosis MH - Chromatography, Liquid MH - Female MH - Humans MH - Infant, Newborn MH - *Malnutrition MH - *Maternal Exposure MH - Methylmalonic Acid MH - Neonatal Screening MH - Pregnancy MH - *Tandem Mass Spectrometry MH - *Vitamin B 12 Deficiency PMC - PMC7277087 OTO - NOTNLM OT - LC-MS/MS OT - false-positive OT - mass spectrometry OT - maternal defects OT - methylmalonic acidemia OT - newborn screening OT - organic acidemias OT - vitamin B12 deficiency COIS- The authors declare no conflict of interest. EDAT- 2020/05/24 06:00 MHDA- 2020/10/21 06:00 PMCR- 2020/05/01 CRDT- 2020/05/24 06:00 PHST- 2020/04/27 00:00 [received] PHST- 2020/05/16 00:00 [revised] PHST- 2020/05/17 00:00 [accepted] PHST- 2020/05/24 06:00 [entrez] PHST- 2020/05/24 06:00 [pubmed] PHST- 2020/10/21 06:00 [medline] PHST- 2020/05/01 00:00 [pmc-release] AID - ijerph17103601 [pii] AID - ijerph-17-03601 [pii] AID - 10.3390/ijerph17103601 [doi] PST - epublish SO - Int J Environ Res Public Health. 2020 May 20;17(10):3601. doi: 10.3390/ijerph17103601.