LABSIEM – Laboratory for the Study of Inborn Errors of Metabolism
UOC Pediatric Clinic and Endocrinology
Head: Prof. M. Maghnie
The laboratory is at the forefront of advancing newborn screening through a seamless integration of biochemical, genomic, and structural-biology approaches, underpinned by clinical research, to detect, diagnose, and understand rare endocrine and metabolic disorders as early as possible.
At its core, the lab drives innovation in first- and second-tier biochemical assays, using cutting-edge FIA‑MS/MS and LC‑MS/MS methods to quantify a wide array of biomolecules: B‑group vitamins, pterins, steroids, lysophosphatidylcholines, acylcarnitines, very long-chain fatty acids, sulfatides, lysosphingolipids, and glycosaminoglycans. These assays not only enhance conventional newborn screening but also facilitate the introduction of novel biomarkers, such as those for β‑oxidation defects, through rigorous validation against enzyme-activity tests.
Simultaneously, the group pioneers the integration of whole‑genome sequencing (WGS) into confirmatory workflows. By tightly comparing genomic data with biochemical 2‑TT results, they validate both biomarker-based diagnostics and emerging genomic assays. This synergy supports the advancement of robust enzyme-activity methods and the identification of new molecular indicators for rare diseases.
Complementing these efforts, the lab cultivates biomolecular genetic methodologies for conditions like SMA and SCID, and investigates sustainable strategies for genomic newborn screening, targeting treatable endocrine and rare disorders at the earliest stage. Parallel to this, it conducts in‑depth molecular and functional genetics research on pediatric endocrine/metabolic conditions, such as neonatal diabetes, Wolfram Syndrome, MODY, hyperinsulinism, familial renal glucosuria, and diabetes insipidus—characterizing point variants via biochemical assays and computational modeling of protein-structure alterations.
Bridging discovery and application, the laboratory also leads pivotal clinical trials—including a Phase III study of vosoritide for hypochondroplasia and a Phase II/III trial of Atumelnant in congenital adrenal hyperplasia, thereby translating its diagnostic innovations into therapeutic advances.
In summary the lab integrates cutting-edge biochemical assays, genomic technologies, and structural biology to elevate newborn screening and rare disease diagnostics. From developing next-generation MS/MS approaches to anchoring validation in whole-genome data, and from characterizing monogenic diabetes genes to running interventional trials, the group occupies a uniquely interdisciplinary niche, championing early detection and intervention for vulnerable pediatric populations. By combining state-of-the-art biochemical screening, genomic validation, functional genetics, and clinical trial expertise, the laboratory creates a powerful, interdisciplinary pipeline. From newborn screening assay development to the in‑depth molecular understanding of rare diseases, and their potential treatment,the group champions early detection, precise diagnosis, and improved outcomes for vulnerable pediatric populations.
Thematic Area
Research and development in the field of newborn screening, biochemistry and genetics of inborn errors of metabolism, genetics of endocrine diseases, and dysglycemia-related pathologies.
Research area
Development of first-tier biochemical methods (1TT), second-tier tests (2TT) and diagnostic confirmation applied to Newborn Screening:
- Development of methods using FIA-MS/MS and LC-MS/MS for quantification of:
- B-group vitamins (B2 and B12 in their various bioavailable forms) to distinguish vitamin deficiencies from certain genetic disorders
- Pterins (neopterin, biopterin, sepiapterin, primapterin) for the differential diagnosis of hyperphenylalaninemias
- Steroids (17-hydroxyprogesterone, androstenedione, cortisol, 21-deoxycortisol, 11-deoxycortisol) for congenital adrenal hyperplasia
- Lysophosphatidylcholines (C20 LPC, C22 LPC, C24 LPC, C26 LPC), acylcarnitines (C24, C26, C16DC, C18DC), very long-chain fatty acids (VLCFAs), phytanic and pristanic acid for peroxisomal disorders
- Sulfatides (C16:0, C16:1, C16:0-OH, C16:1-OH) and ARSA enzyme activity for metachromatic leukodystrophy
- Lysosphingolipids (Lyso GB1, Lyso GB3, psychosine, Lyso SM, Lyso SM509, GAGs) for lysosomal storage diseases
- New second-tier markers (2TT) for β-oxidation defects
- Comparison of WGS and biochemical 2TT results for validation of biochemical second-tier tests
- Development of assays for enzyme-activity determination and/or new biomarkers for diseases included in Newborn Screening
- Development of biomolecular methods applicable to SMA and SCID Newborn Screening
- Development of sustainable strategies for Genomic Newborn Screening aimed at the early diagnosis of endocrine, rare, and potentially treatable diseases
- Molecular study and characterization of genes responsible for neonatal diabetes mellitus, Wolfram Syndrome, pediatric-onset monogenic diabetes mellitus (MODY), hyperinsulinism, familial renal glucosuria, diabetes insipidus, and other metabolic disorders
- Functional study and characterization of point variants (intronic and regulatory) of unknown biological significance
- Computational analysis and characterization of protein-structure alterations caused by point variants in disease-causing genes.
Clinical trials conducted:
- A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Vosoritide in Children with Hypochondroplasia
- A Phase 2/3 Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of Atumelnant Treatment in Pediatric Participants with Congenital Adrenal Hyperplasia, Including a Long-Term Extension
Staff
Responsible: Prof Mohamad Maghnie
Biochemistry Research Sector
Contact Person: Dr. Michela Perrone Donnorso, Technical Officer, PhD, specialized in Clinical Pathology and Biochemistry, IRCCS DINOGMI, University of Genoa
Administrative Staff: Ms. Stefania Bertoni, Administrative Assistant, DINOGMI, University of Genoa
Technical Staff: Mr. Andrea Mascagni, Technical Officer, DINOGMI, University of Genoa
Molecular Biology & Genetics Research Sector
Dr. Concetta Aloi, Research Scientist (Healthcare), PhD, specialized in Clinical Pathology, IRCCS Istituto Giannina Gaslini
Dr. Alessandro Salina, Research Scientist (Healthcare), PhD, Genetics Resident, IRCCS Istituto Giannina Gaslini
Existing Collaborations
Integration of research and development activities applied to Newborn Screening programs with the Regional Reference Screening Laboratory:
UOS Biochemistry, Pharmacology and Newborn Screening – UOC Central Analysis Laboratory – IRCCS G. Gaslini Institute
https://www.gaslini.org/reparti/laboratorio-analisi
Screening Sector Contact: Dr. Michela Cassanello
UOC Medical Genetics, IRCCS G. Gaslini Institute
https://www.gaslini.org/reparti/genetica-medica/
UOC Genomics and Clinical Genetics, IRCCS G. Gaslini Institute
https://www.gaslini.org/reparti/genomica-e-genetica-clinica/
Bioinformatics Unit, IRCCS G. Gaslini Institute
Genomics Facility (GEFA), Italian Institute of Technology – IIT, Genoa
https://gefa.iit.it/
Prof. Mohamad Maghnie, MD, PhD
Full Professor of Pediatrics and Director of the Pediatric Residency Program, University of Genoa
Director, UOC Pediatric Clinic, Endocrinology
Director, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics and Maternal-Infant Sciences (DINOGMI)
IRCCS Giannina Gaslini Institute
Via Gerolamo Gaslini 5, 16147 Genoa, Italy
University of Genoa
National Coordinator, ENDO ERN – Italian Society of Pediatric Endocrinology and Diabetology
Email: MohamadMaghnie@gaslini.org; Mohamad.Maghnie@unige.it