Classification of Congenital Leptin Deficiency.

Autor:	von Schnurbein J; Division of Paediatric Endocrinology and Diabetes, Department of Paediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, 89075, Germany., Zorn S; Division of Paediatric Endocrinology and Diabetes, Department of Paediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, 89075, Germany., Nunziata A; Division of Paediatric Endocrinology and Diabetes, Department of Paediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, 89075, Germany., Brandt S; Division of Paediatric Endocrinology and Diabetes, Department of Paediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, 89075, Germany., Moepps B; Institute of Experimental and Clinical Pharmacology, Toxicology and Pharmacology of Natural Products, Ulm University Medical Center, Ulm, 89075, Germany., Funcke JB; Division of Paediatric Endocrinology and Diabetes, Department of Paediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, 89075, Germany.; Touchstone Diabetes Center, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Hussain K; Division of Endocrinology, Department of Pediatrics, Sidra Medicine, OPC, C6-340, PO Box 26999, Doha, Qatar., Farooqi IS; Wellcome Trust-MRC Institute of Metabolic Science and NIHR Cambridge Biomedical Research Centre, Addenbrooke's Hospital, Cambridge, CB2 0QQ, UK., Fischer-Posovszky P; Division of Paediatric Endocrinology and Diabetes, Department of Paediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, 89075, Germany., Wabitsch M; Division of Paediatric Endocrinology and Diabetes, Department of Paediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, 89075, Germany.
Jazyk:	angličtina
Zdroj:	The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 2024 Sep 16; Vol. 109 (10), pp. 2602-2616.
DOI:	10.1210/clinem/dgae149
Abstrakt:	Purpose: Biallelic pathogenic leptin gene variants cause severe early-onset obesity usually associated with low or undetectable circulating leptin levels. Recently, variants have been described resulting in secreted mutant forms of the hormone leptin with either biologically inactive or antagonistic properties. Methods: We conducted a systematic literature research supplemented by unpublished data from patients at our center as well as new in vitro analyses to provide a systematic classification of congenital leptin deficiency based on the molecular and functional characteristics of the underlying leptin variants and investigated the correlation of disease subtype with severity of the clinical phenotype. Results: A total of 28 distinct homozygous leptin variants were identified in 148 patients. The identified variants can be divided into 3 different subtypes of congenital leptin deficiency: classical hormone deficiency (21 variants in 128 patients), biologically inactive hormone (3 variants in 12 patients), and antagonistic hormone (3 variants in 7 patients). Only 1 variant (n = 1 patient) remained unclassified. Patients with biological inactive leptin have a higher percentage of 95th body mass index percentile compared to patients with classical hormone deficiency. While patients with both classical hormone deficiency and biological inactive hormone can be treated with the same starting dose of metreleptin, patients with antagonistic hormone need a variant-tailored treatment approach to overcome the antagonistic properties of the variant leptin. Main Conclusion: Categorization of leptin variants based on molecular and functional characteristics helps to determine the most adequate approach to treatment of patients with congenital leptin deficiency. (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)
Databáze:	MEDLINE
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