Newborn Screening for Biotinidase Deficiency. The Experience of a Regional Center in Italy

Maguolo, Alice; Rodella, Giulia; Dianin, Alice; Monge, Irene; Messina, Martina; Rigotti, E; Pellegrini, Francesca; Molinaro, Grazia; Lupi, Fiorenzo; Pasini, Andrea; Campostrini, Natascia; Popa, Florina; Teofoli, Francesca; Vincenzi, Monica; Camilot, Marta; Piacentini, Giorgio; Bordugo, Andrea

doi:10.3389/fped.2021.661416

Cited by 18 publications

(13 citation statements)

References 25 publications

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“…This mutation has a high prevalence among the European population and was also reported in other regions of the world. 63 These results indicate, that D444H is the common variant in BTD gene and that may be used as a biomarker for the purpose of prenatal diagnosis.…”

Section: Mutations In Other Populationsmentioning

confidence: 78%

A Rare Biotinidase Deficiency in the Pediatrics Population: Genotype–Phenotype Analysis

et al. 2022

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Biotinidase (BTD) deficiency is a rare autosomal recessive metabolic disorder caused by insufficient biotin metabolism, where it cannot recycle the vitamin biotin. When this deficiency is not treated with supplements, it can lead to severe neurological conditions. Approximately 1 in 60,000 newborns are affected by BTD deficiency. The BTD deficiency causes late-onset biotin-responsive multiple carboxylase deficiency, which leads to acidosis or lactic acidosis, hypoglycemia, and abnormal catabolism. BTD deficiency is of two types based on the amount of BTD Enzyme present in the serum. A wide range of pathogenic mutations in the BTD gene are reported worldwide. Mutations in the BTD gene lead to profound and partial BTD deficiency. Profound BTD deficiency results in a severe pathogenic condition. A high frequency of newborns are affected with the partial deficiency worldwide. They are mostly asymptomatic, but symptoms may appear during stressful conditions such as fasting or viral infections. Several pathogenic mutations are significantly associated with neurological, ophthalmological, and skin problems along with several other clinical features. This review discusses the BTD gene mutation in multiple populations detected with phenotypic features. The molecular-based biomarker screening is necessary for the disease during pregnancy, as it could be helpful for the early identification of BTD deficiency, providing a better treatment strategy. Moreover, implementing newborn screening for the BTD deficiency helps patients prevent several diseases.

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Section: Mutations In Other Populationsmentioning

confidence: 78%

A Rare Biotinidase Deficiency in the Pediatrics Population: Genotype–Phenotype Analysis

et al. 2022

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“…In Italy, the following incidences have been reported: combined profound BD between 1:61,000 and 1:6215 and partial BD between 1:137,236 and 1:7172 [12,26]. In a recent work, a higher incidence has been reported: 1:58,757 profound DB and 1:6677 partial BD [13].…”

Section: Discussionmentioning

confidence: 92%

“…Changes in the method for BTD activity assay from colorimetric to the more sensitive fluorometric can also lead to increased detection rate of the screening programs over time [9]. In the more recent studies, a higher incidence has been reported in some countries, such as Brazil, Turkey, and Italy [6,[10][11][12][13][14]. The clinical presentation of BD is variable mostly in relation to the degree of the residual enzyme activity, although different expressions in a family with the same genotype has been reported [5,6].…”

Section: Introductionmentioning

confidence: 99%

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

Semeraro

Verrocchio

Dalmazi

et al. 2022

IJERPH

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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.

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“…The development of mass spectrometry led to numerous pilot projects during the last two decades. Reports on regional NBS programs including those based on MS/MS have been published [ 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

Expanded Newborn Screening in Italy Using Tandem Mass Spectrometry: Two Years of National Experience

Ruoppolo

Malvagia

Boenzi

et al. 2022

IJNS

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Newborn screening (NBS) for inborn errors of metabolism is one of the most advanced tools for secondary prevention in medicine, as it allows early diagnosis and prompt treatment initiation. The expanded newborn screening was introduced in Italy between 2016 and 2017 (Law 167/2016; DM 13 October 2016; DPCM 12-1-2017). A total of 1,586,578 infants born in Italy were screened between January 2017 and December 2020. For this survey, we collected data from 15 Italian screening laboratories, focusing on the metabolic disorders identified by tandem mass spectrometry (MS/MS) based analysis between January 2019 and December 2020. Aminoacidemias were the most common inborn errors in Italy, and an equal percentage was observed in detecting organic acidemias and mitochondrial fatty acids beta-oxidation defects. Second-tier tests are widely used in most laboratories to reduce false positives. For example, second-tier tests for methylmalonic acid and homocysteine considerably improved the screening of CblC without increasing unnecessary recalls. Finally, the newborn screening allowed us to identify conditions that are mainly secondary to a maternal deficiency. We describe the goals reached since the introduction of the screening in Italy by exchanging knowledge and experiences among the laboratories.

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Newborn Screening for Biotinidase Deficiency. The Experience of a Regional Center in Italy

Cited by 18 publications

References 25 publications

A Rare Biotinidase Deficiency in the Pediatrics Population: Genotype–Phenotype Analysis

A Rare Biotinidase Deficiency in the Pediatrics Population: Genotype–Phenotype Analysis

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

Expanded Newborn Screening in Italy Using Tandem Mass Spectrometry: Two Years of National Experience

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