silvia funghini

@meyer.it

aou meyer



           

https://researchid.co/s.funghini

RESEARCH, TEACHING, or OTHER INTERESTS

Biochemistry, Genetics and Molecular Biology, Biochemistry (medical)

43

Scopus Publications

Scopus Publications

  • Expanded Newborn Screening in Italy Using Tandem Mass Spectrometry: Two Years of National Experience
    Margherita Ruoppolo, Sabrina Malvagia, Sara Boenzi, Carla Carducci, Carlo Dionisi-Vici, Francesca Teofoli, Alberto Burlina, Antonio Angeloni, Tommaso Aronica, Andrea Bordugo,et al.
    MDPI AG
    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.

  • Lysosomals
    Silvia Funghini, Sabrina Malvagia, Giulia Polo, and Giancarlo la Marca
    Springer International Publishing

  • The successful inclusion of ADA SCID in Tuscany expanded newborn screening program
    Sabrina Malvagia, Silvia Funghini, Maria Della Bona, Daniela Ombrone, Massimo Mura, Roberta Damiano, Silvia Ricci, Martina Cortimiglia, Chiara Azzari, and Giancarlo la Marca
    Walter de Gruyter GmbH

  • High frequency of biotinidase deficiency in Italian population identified by newborn screening
    Silvia Funghini, Rodolfo Tonin, Sabrina Malvagia, Anna Caciotti, Maria Alice Donati, Amelia Morrone, and Giancarlo la Marca
    Elsevier BV

  • A new strategy implementing mass spectrometry in the diagnosis of congenital disorders of N-glycosylation (CDG)
    Bruno Casetta, Sabrina Malvagia, Silvia Funghini, Diego Martinelli, Carlo Dionisi-Vici, Rita Barone, Agata Fiumara, Maria Alice Donati, Renzo Guerrini, and Giancarlo la Marca
    Walter de Gruyter GmbH
    Abstract Objectives Congenital disorders of N-glycosylation (CDG) are a large group of rare metabolic disorders caused by defects in the most common post-translational modification of proteins. CDGs are often difficult to diagnose as they are manifested with non-specific symptoms and signs. Analysis of serum transferrin (TRF) isoforms, as the classical procedure used to identify a CDG patient, enables to predict pathological steps in the N-linked glycosylation process. Methods We devised a new strategy based on liquid chromatography-mass spectrometry (LC-MS) for the analysis of TRF isoforms by combining a simple and fast sample preparation with a specific chromatographic cleanup/separation step followed by mass-spectrometric measurement. Single TRF isoform masses were obtained through reconstruction of multiply charged electrospray data collected by quadrupole-MS technology. Hereby, we report the first analyzed serum samples obtained from 20 CDG patients and 100 controls. Results The ratio of desialylated isoforms to total TRF was calculated for patients and controls. CDG-Type I patients showed higher amounts of bi-sialo isoform (range: 6.7–29.6%) compared to controls (<5.5%, mean percentage 3.9%). CDG-Type II pattern showed an increased peak of tri-sialo isoforms. The mean percentage of tri-sialo-TRF was 9.3% (range: 2.9–12.9%) in controls, which was lower than that obtained from two patients with COG5-CDG and MAN1B1-CDG (18.5 and 24.5%). Intraday and between-day imprecisions were less than 9 and 16%, respectively, for bi-sialo- and less than 3 and 6% for tri-sialo-TRF. Conclusions This LC-MS-based approach provides a simple, sensitive and fast analytical tool for characterizing CDG disorders in a routine clinical biochemistry while improving diagnostic accuracy and speeding clinical decision-making.

  • Development of a fast LC-MS/MS protocol for combined measurement of six LSDs on dried blood spot in a newborn screening program
    Emanuela Scolamiero, Bruno Casetta, Sabrina Malvagia, Tetsuo Tanigawa, Giulia Forni, Silvia Funghini, Massimo Mura, Francesca Raspini, Sara Poggiali, and Giancarlo la Marca
    Elsevier BV

  • LC-MS/MS method for simultaneous quantification of heparan sulfate and dermatan sulfate in urine by butanolysis derivatization
    Giulia Forni, Sabrina Malvagia, Silvia Funghini, Emanuela Scolamiero, Massimo Mura, Maria Della Bona, Fabio Villanelli, Roberta Damiano, and Giancarlo la Marca
    Elsevier BV

  • Data in support for the measurement of heparan sulfate and dermatan sulfate by LC–MS/MS analysis
    Giulia Forni, Sabrina Malvagia, Silvia Funghini, Emanuela Scolamiero, Massimo Mura, Maria Della Bona, Fabio Villanelli, Roberta Damiano, and Giancarlo la Marca
    Elsevier BV

  • Late-onset n-acetylglutamate synthase deficiency: Report of a paradigmatic adult case presenting with headaches and review of the literature
    Catia Cavicchi, Chiara Chilleri, Antonella Fioravanti, Lorenzo Ferri, Francesco Ripandelli, Cinzia Costa, Paolo Calabresi, Paolo Prontera, Francesca Pochiero, Elisabetta Pasquini,et al.
    MDPI AG
    N-acetylglutamate synthase deficiency (NAGSD) is an extremely rare urea cycle disorder (UCD) with few adult cases so far described. Diagnosis of late-onset presentations is difficult and delayed treatment may increase the risk of severe hyperammonemia. We describe a 52-year-old woman with recurrent headaches who experienced an acute onset of NAGSD. As very few papers focus on headaches in UCDs, we also report a literature review of types and pathophysiologic mechanisms of UCD-related headaches. In our case, headaches had been present since puberty (3–4 days a week) and were often accompanied by nausea, vomiting, or behavioural changes. Despite three previous episodes of altered consciousness, ammonia was measured for the first time at 52 years and levels were increased. Identification of the new homozygous c.344C>T (p.Ala115Val) NAGS variant allowed the definite diagnosis of NAGSD. Bioinformatic analysis suggested that an order/disorder alteration of the mutated form could affect the arginine-binding site, resulting in poor enzyme activation and late-onset presentation. After optimized treatment for NAGSD, ammonia and amino acid levels were constantly normal and prevented other headache bouts. The manuscript underlies that headache may be the presenting symptom of UCDs and provides clues for the rapid diagnosis and treatment of late-onset NAGSD.

  • SSADH deficiency in an Italian family: a novel ALDH5A1 gene mutation affecting the succinic semialdehyde substrate binding site
    Sara Leo, Concetta Capo, Bianca Maria Ciminelli, Federico Iacovelli, Giovanna Menduti, Silvia Funghini, Maria Alice Donati, Mattia Falconi, Luisa Rossi, and Patrizia Malaspina
    Springer Science and Business Media LLC

  • Clinical relevance of short-chain acyl-CoA dehydrogenase (SCAD) deficiency: Exploring the role of new variants including the first SCAD-disease-causing allele carrying a synonymous mutation
    Rodolfo Tonin, Anna Caciotti, Silvia Funghini, Elisabetta Pasquini, Sean D. Mooney, Binghuang Cai, Elena Proncopio, Maria Alice Donati, Federico Baronio, Ilaria Bettocchi,et al.
    Elsevier BV

  • Reducing the false-positive rate for isovalerylcarnitine in expanded newborn screening: The application of a second-tier test
    Sara Poggiali, Daniela Ombrone, Giulia Forni, Sabrina Malvagia, Silvia Funghini, Massimo Mura, Elisabetta Pasquini, Laura Santoro, Vincenzo Bellavia, Orazia Maria Granata,et al.
    FapUNIFESP (SciELO)
    The isodecyl neopentanoate is an ingredient used in the cosmetic industry to prepare a nipple fissure balm. We report on 12 newborns that showed elevated C5-acylcarnitine levels upon newborn screening following treatment with balm. The first 3 neonates were immediately recalled for confirmatory tests and resulted negative for both isovaleric acidemia and short/branched chain acyl-CoA dehydrogenase deficiency. In the other 9 cases, the immediate recall was avoided by applying a new second-tier test able to confirm the presence of pivaloylcarnitine. The concentration of C5-acylcarnitine was measured in the days following the suspension of balm application. Abnormal concentrations of C5-acylcarnitine did not seem to be associated with free carnitine deficiency, probably due to the short time of exposure. A direct correlation between balm ingestion and the elevation in pivaloylcarnitine has been demonstrated in 10 adult volunteers. The commercial balm containing a pivalic acid derivative is causal of false-po...

  • Development and validation of a 2nd tier test for identification of purine nucleoside phosphorylase deficiency patients during expanded newborn screening by liquid chromatography-tandem mass spectrometry
    Giancarlo la Marca, Elisa Giocaliere, Sabrina Malvagia, Fabio Villanelli, Silvia Funghini, Daniela Ombrone, Maria Della Bona, Giulia Forni, Clementina Canessa, Silvia Ricci,et al.
    Walter de Gruyter GmbH
    AbstractPurine nucleoside phosphorylase (PNP) deficiency has been recently introduced in the newborn screening program in Tuscany. In order to improve the PNP screening efficiency, we developed a 2nd tier test to quantify PNP primary markers deoxyguanosine (dGuo) and deoxyinosine (dIno).Dried blood spots (DBS) samples were extracted with 200 μL of methanol and 100 μL of water (by two steps). Internal standards were added at a final concentration of 10 μmol/L. After extraction, samples were analysed by LC-MS/MS. The chromatographic run was performed in gradient mode by using a Synergi Fusion column.The assay was linear over a concentration range of 0.05–50 μmol/L (RThe LC-MS/MS method can reliably measure dIno and dGuo in DBS for the diagnosis of PNP. Validation data confirm the present method is characterised by good reproducibility, accuracy and imprecision for the quantitation of dIno and dGuo. The assay also appears suitable for use in monitoring treatment of PNP patients.

  • Intra-individual plasticity of the TAZ gene leading to different heritable mutations in siblings with Barth syndrome
    Lorenzo Ferri, Maria A Donati, Silvia Funghini, Catia Cavicchi, Viviana Pensato, Cinzia Gellera, Federica Natacci, Luigina Spaccini, Serena Gasperini, Frédéric M Vaz,et al.
    Springer Science and Business Media LLC

  • Heptadecanoylcarnitine (C17) a novel candidate biomarker for newborn screening of propionic and methylmalonic acidemias
    Sabrina Malvagia, Christopher A. Haynes, Laura Grisotto, Daniela Ombrone, Silvia Funghini, Elisa Moretti, Kathleen S. McGreevy, Annibale Biggeri, Renzo Guerrini, Raquel Yahyaoui,et al.
    Elsevier BV

  • Biotinidase deficiency due to a de novo mutation or gonadal mosaicism in a first child
    Rodolfo Tonin, Anna Caciotti, Silvia Funghini, Giancarlo la Marca, Elisabetta Pasquini, Erica Cayton, Sean D. Mooney, Renzo Guerrini, and Amelia Morrone
    Elsevier BV

  • Therapeutic drug monitoring of carbamazepine and its metabolite in children from dried blood spots using liquid chromatography and tandem mass spectrometry
    Engy Shokry, Fabio Villanelli, Sabrina Malvagia, Anna Rosati, Giulia Forni, Silvia Funghini, Daniela Ombrone, Maria Della Bona, Renzo Guerrini, and Giancarlo la Marca
    Elsevier BV

  • Dried blood spot assay for the quantification of phenytoin using Liquid Chromatography-Mass Spectrometry
    Fabio Villanelli, Elisa Giocaliere, Sabrina Malvagia, Anna Rosati, Giulia Forni, Silvia Funghini, Engy Shokry, Daniela Ombrone, Maria Luisa Della Bona, Renzo Guerrini,et al.
    Elsevier BV

  • Sudden unexpected fatal encephalopathy in adults with OTC gene mutations-Clues for early diagnosis and timely treatment
    Catia Cavicchi, Maria Alice Donati, Rossella Parini, Miriam Rigoldi, Mauro Bernardi, Francesca Orfei, Nicolò Gentiloni Silveri, Aniello Colasante, Silvia Funghini, Serena Catarzi,et al.
    Springer Science and Business Media LLC

  • The inclusion of ADA-SCID in expanded newborn screening by tandem mass spectrometry
    Giancarlo la Marca, Elisa Giocaliere, Sabrina Malvagia, Silvia Funghini, Daniela Ombrone, Maria Luisa Della Bona, Clementina Canessa, Francesca Lippi, Francesca Romano, Renzo Guerrini,et al.
    Elsevier BV

  • Aminoacylase I deficiency due to ACY1 mRNA exon skipping
    L. Ferri, S. Funghini, A. Fioravanti, E.G. Biondi, G. la Marca, R. Guerrini, M.A. Donati, and A. Morrone
    Wiley
    Aminoacylase 1 (ACY1) deficiency is a rare inborn error of metabolism of which less than 20 observations have been described. Patients exhibit urinary excretion of specific N‐acetyl amino acids and manifest a heterogeneous clinical spectrum including intellectual disability, motor delay, seizures, moderate to severe mental retardation, absent speech, growth delay, muscular hypotonia and autistic features. Here, we report the case of ACY1 enzyme deficiency in a 6‐year‐old girl presenting severe intellectual disability, motor retardation, absence of spontaneous locomotor activity and severe speech delay. Urinary excretion of N‐acetylated amino acids was present. Mutational analysis of ACY1 gene identified the new homozygous c.1001_1001+5del6 mutation, which alters the mRNA transcription leading to exon 13 skipping and inclusion of a premature stop codon (p.Lys308Glufs*7). A quantitative fluorescent multiplex‐polymerase chain reaction (QFM‐PCR) assay has been set up and confirmed homozygosity of the mutation in the patient's DNA. Biochemical analysis showed absence of ACY1 enzyme activity in the patient's fibroblasts. The structure of the mutated protein has been defined by homology modeling (HM). Our data endorse the hypothesis of a link between this inborn error of metabolism and the neurological manifestations observed in patients with ACY1 deficiency.

  • Diagnosis of immunodeficiency caused by a purine nucleoside phosphorylase defect by using tandem mass spectrometry on dried blood spots
    Giancarlo la Marca, Clementina Canessa, Elisa Giocaliere, Francesca Romano, Sabrina Malvagia, Silvia Funghini, Maria Moriondo, Claudia Valleriani, Francesca Lippi, Daniela Ombrone,et al.
    Elsevier BV

  • Tandem mass spectrometry, but not T-cell receptor excision circle analysis, identifies newborns with late-onset adenosine deaminase deficiency
    Giancarlo la Marca, Clementina Canessa, Elisa Giocaliere, Francesca Romano, Marzia Duse, Sabrina Malvagia, Francesca Lippi, Silvia Funghini, Leila Bianchi, Maria Luisa Della Bona,et al.
    Elsevier BV

  • A rapid liquid chromatography tandem mass spectrometry-based method for measuring propranolol on dried blood spots
    Maria Luisa Della Bona, Sabrina Malvagia, Fabio Villanelli, Elisa Giocaliere, Daniela Ombrone, Silvia Funghini, Luca Filippi, Giacomo Cavallaro, Paola Bagnoli, Renzo Guerrini,et al.
    Elsevier BV

  • Screening of lysosomal storage disorders: Application of the online trapping-and-cleanup liquid chromatography/mass spectrometry method for mucopolysaccharidosis i
    Daniela Ombrone, Sabrina Malvagia, Silvia Funghini, Elisa Giocaliere, Maria Luisa Della Bona, Giulia Forni, Alessio De Luca, Fabio Villanelli, Bruno Casetta, Renzo Guerrini,et al.
    SAGE Publications
    In recent years, new treatments have become available to treat some lysosomal storage disorders (LSDs) and many studies suggest that there is a benefit with starting therapy early. Newborn screening should detect diseases early enough for prompt treatment. Some countries include additional conditions, such as some LSDs, into their newborn screening panels. Mucopolysaccharidosis Type I (MPS I) is an autosomal recessive disorder caused by the deficiency of α-L-iduronidase (IDUA) activity. Currently, enzyme replacement therapy (ERT) or bone marrow transplantation is available and this has raised a growing interest for the development of a newborn screening test. In 2009, we reported a new fast and simplified tandem mass spectrometry-based method for quantifying five enzyme activities on dried blood spots. Here, we describe the inclusion of IDUA activity determination for the simultaneous detection of six lysosomal storage diseases. We have defined reference normal ranges by testing 680 healthy newborns and 240 adults. The assay was checked through three confirmed MPS I patients whose IDUA activity was below the normal range. Reproducibility of the assays has been established by assessing the intra-day and inter-day assay imprecisions. This quick assay has been devised to be implemented in newborn screening by liquid chromatography tandem mass spectrometry.