Metabolic profiling of Costello syndrome: Insights from a single-center cohort

Chiara Leoni; Miriam Massese; Jacopo Gervasoni; Aniello Primiano; Valentina Giorgio; Roberta Onesimo; Eliza Kuczynska; Donato Rigante; Silvia Persichilli; Giovanna Carpentieri; Elisabetta Flex; Roberta Pastorino; Marco Tartaglia; Giuseppe Zampino

doi:10.1016/j.ejmg.2022.104439

Metabolic profiling of Costello syndrome: Insights from a single-center cohort

Eur J Med Genet. 2022 Mar;65(3):104439. doi: 10.1016/j.ejmg.2022.104439. Epub 2022 Jan 29.

Affiliations

¹ Center for Rare Diseases and Birth Defects, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy. Electronic address: chiara.leoni@policlinicogemelli.it.
² Center for Rare Diseases and Birth Defects, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
³ Department of Laboratory and Infectious Diseases, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
⁴ Department of Laboratory and Infectious Diseases, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy; Università Cattolica Sacro Cuore, Rome, Italy.
⁵ Center for Rare Diseases and Birth Defects, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy; Università Cattolica Sacro Cuore, Rome, Italy.
⁶ Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, Italy; Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
⁷ Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
⁸ Department of Woman and Child Health and Public Health - Public Health Area, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
⁹ Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, Italy.

PMID: 35101635
DOI: 10.1016/j.ejmg.2022.104439

Abstract

Costello syndrome (CS) is a rare disorder caused by activating dominantly acting germline variants in the HRAS gene. CS is defined by a clinical phenotype characterized by a distinctive gestalt, multiple congenital anomalies, and increased risk to develop tumors. Hypoglycemia and hypercholesterolemia have been reported to occur in affected individuals, but the underlying molecular events remain to be characterized. Here, we provided data on glucose/lipid metabolism and amino acid profile of a large single-center cohort of individuals affected by CS to systematically assess the extent of metabolic dysregulation characterizing this disorder and optimize patient management.

Keywords: Biomarker; Costello syndrome; Hypoglycemia; Metabolism tracer; Personalized medicine.

MeSH terms

Abnormalities, Multiple* / genetics
Cohort Studies
Costello Syndrome* / genetics
Costello Syndrome* / pathology
Humans
Hypoglycemia*
Phenotype
Proto-Oncogene Proteins p21(ras) / genetics

Substances

Proto-Oncogene Proteins p21(ras)