High Incidence of Partial Biotinidase Deficiency in the First 3 Years of a Regional Newborn Screening Program in Italy

Daniela Semeraro, Sara Verrocchio, Giulia Di Dalmazi, Claudia Rossi, Damiana Pieragostino, Ilaria Cicalini, Rossella Ferrante, Silvia Di Michele, Liborio Stuppia, Cristiano Rizzo, Francesca Romana Lepri, Antonio Novelli, Carlo Dionisi-Vici, Vincenzo De Laurenzi and Ines Bucci
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Daniela Semeraro: Center for Advanced Studies and Technology (CAST), “G. d’Annunzio” University of Chieti-Pescara, 66100 Chieti, Italy
Sara Verrocchio: Center for Advanced Studies and Technology (CAST), “G. d’Annunzio” University of Chieti-Pescara, 66100 Chieti, Italy
Giulia Di Dalmazi: Center for Advanced Studies and Technology (CAST), “G. d’Annunzio” University of Chieti-Pescara, 66100 Chieti, Italy
Claudia Rossi: Center for Advanced Studies and Technology (CAST), “G. d’Annunzio” University of Chieti-Pescara, 66100 Chieti, Italy
Damiana Pieragostino: Center for Advanced Studies and Technology (CAST), “G. d’Annunzio” University of Chieti-Pescara, 66100 Chieti, Italy
Ilaria Cicalini: Center for Advanced Studies and Technology (CAST), “G. d’Annunzio” University of Chieti-Pescara, 66100 Chieti, Italy
Rossella Ferrante: Center for Advanced Studies and Technology (CAST), “G. d’Annunzio” University of Chieti-Pescara, 66100 Chieti, Italy
Silvia Di Michele: Department of Pediatrics, “Spirito Santo” Hospital, 65124 Pescara, Italy
Liborio Stuppia: Center for Advanced Studies and Technology (CAST), “G. d’Annunzio” University of Chieti-Pescara, 66100 Chieti, Italy
Cristiano Rizzo: Division of Metabolism, Bambino Gesù Children’s Research Hospital, 00165 Rome, Italy
Francesca Romana Lepri: Translational Cytogenomics Research Unit, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy
Antonio Novelli: Translational Cytogenomics Research Unit, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy
Carlo Dionisi-Vici: Division of Metabolism, Bambino Gesù Children’s Research Hospital, 00165 Rome, Italy
Vincenzo De Laurenzi: Center for Advanced Studies and Technology (CAST), “G. d’Annunzio” University of Chieti-Pescara, 66100 Chieti, Italy
Ines Bucci: Center for Advanced Studies and Technology (CAST), “G. d’Annunzio” University of Chieti-Pescara, 66100 Chieti, Italy

IJERPH, 2022, vol. 19, issue 13, 1-12

Abstract: Biotinidase deficiency (BD) is an autosomal recessive inherited disorder in which the enzyme biotinidase is totally or partially defective and the vitamin biotin is not recycled. BD meets the major criteria for a population screening program. Newborn bloodspot screening (NBS) allows early diagnosis of BD, thus preventing the high morbidity and mortality associated with untreated disease. Both profound and partial BD variant can be detected by NBS test, and serum enzyme activity and/or mutational analysis are required for definitive diagnosis. In Italy, BD is included in the screening panel for inborn errors of metabolism (IEMs) that has been declared mandatory in 2016. We analyzed the data of the first 3 years of the NBS for BD in our region (Abruzzo, Italy), with the aim to describe the outcomes of this recently introduced screening program. In over 26,393 newborns screened, we found 2 carriers and 16 cases with genotype associated with partial BD. Since the serum biotinidase assay has been recently introduced in our algorithm, only three of our newborns met the criteria of genetic and biochemical confirmation, with an incidence of 1:8797, which is in the high range of what has been reported in the literature. All affected infants carried the 1330G>C (D444H) variant in compound heterozygosis, with variants known to be associated with profound BD. A variant previously not described and likely pathogenic was found in one newborn. None of the infants had signs or symptoms. The study of the distribution of the enzyme activity in our population allowed us to validate the adopted cutoff with which the program has a positive predictive value of 18% and to analyze some preanalytical factors influencing biotinidase activity: A correlation of the enzyme activity with gestational age and time at specimen collection was found. Lower mean values of enzyme activity were found in infants born in the summer.

Keywords: newborn blood spot screening; biotinidase deficiency; expanded newborn screening; inborn errors of metabolism; biotinidase gene variants; biotinidase activity (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2022
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