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, Damiana Pieragostino

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number3601
JournalInternational Journal of Environmental Research and Public Health
Volume17
Issue number10
DOIs
Publication statusPublished - May 2 2020

Keywords

  • False-positive
  • LC-MS/MS
  • Mass spectrometry
  • Maternal defects
  • Methylmalonic acidemia
  • Newborn screening
  • Organic acidemias
  • Vitamin B12 deficiency

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Health, Toxicology and Mutagenesis

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