High morbidity and mortality in children with untreated congenital deficiency of leptin or its receptor.

Child Humans Cross-Sectional Studies Leptin Morbidity Obesity, Morbid Retrospective Studies
age-related changes body growth consanguinity leptin-signaling deficiency metabolism monogenic obesity morbidity mortality oxidative stress

Journal

Cell reports. Medicine
ISSN: 2666-3791
Titre abrégé: Cell Rep Med
Pays: United States
ID NLM: 101766894

Informations de publication

Date de publication:
19 09 2023
Historique:
received: 21 03 2023
revised: 29 05 2023
accepted: 11 08 2023
medline: 22 9 2023
pubmed: 3 9 2023
entrez: 2 9 2023
Statut: ppublish

Résumé

The long-term clinical outcomes of severe obesity due to leptin signaling deficiency are unknown. We carry out a retrospective cross-sectional investigation of a large cohort of children with leptin (LEP), LEP receptor (LEPR), or melanocortin 4 receptor (MC4R) deficiency (n = 145) to evaluate the progression of the disease. The affected individuals undergo physical, clinical, and metabolic evaluations. We report a very high mortality in children with LEP (26%) or LEPR deficiency (9%), mainly due to severe pulmonary and gastrointestinal infections. In addition, 40% of surviving children with LEP or LEPR deficiency experience life-threatening episodes of lung or gastrointestinal infections. Although precision drugs are currently available for LEP and LEPR deficiencies, as yet, they are not accessible in Pakistan. An appreciation of the severe impact of LEP or LEPR deficiency on morbidity and early mortality, educational attainment, and the attendant stigmatization should spur efforts to deliver the available life-saving drugs to these children as a matter of urgency.

Identifiants

DOI: 10.1016/j.xcrm.2023.101187 PMID: 37659411 PMC: PMC10518629
pubmed: 37659411
pii: S2666-3791(23)00354-3
doi: 10.1016/j.xcrm.2023.101187
pmc: PMC10518629
pii:
doi:

Substances chimiques

LEP protein, human 0
Leptin 0
LEPR protein, human 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

101187

Subventions

Organisme : Medical Research Council
ID : MR/S026193/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/S026193/1
Pays : United Kingdom

Informations de copyright

Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

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Auteurs

Sadia Saeed (S)

Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK; INSERM UMR 1283, CNRS UMR 8199, European Genomic Institute for Diabetes (EGID), Institut Pasteur de Lille, Lille, France; University of Lille, Lille University Hospital, Lille, France. Electronic address: s.saaed08@imperial.ac.uk.

Roohia Khanam (R)

KAM School of Life Sciences, Forman Christian College, Lahore, Pakistan.

Qasim M Janjua (QM)

Department of Physiology and Biophysics, College of Medicine and Health Sciences, National University of Science and Technology, Sohar, Oman.

Jaida Manzoor (J)

Department of Paediatric Endocrinology, Children's Hospital, Lahore, Pakistan.

Lijiao Ning (L)

INSERM UMR 1283, CNRS UMR 8199, European Genomic Institute for Diabetes (EGID), Institut Pasteur de Lille, Lille, France; University of Lille, Lille University Hospital, Lille, France.

Sharoon Hanook (S)

Department of Statistics, Forman Christian College, Lahore, Pakistan.

Mickaël Canouil (M)

INSERM UMR 1283, CNRS UMR 8199, European Genomic Institute for Diabetes (EGID), Institut Pasteur de Lille, Lille, France; University of Lille, Lille University Hospital, Lille, France.

Muhammad Ali (M)

Paediatric Endocrinology, Mayo Hospital, Lahore, Pakistan.

Hina Ayesha (H)

Department of Paediatrics, Punjab Medical College, Faisalabad, Pakistan.

Waqas I Khan (WI)

The Children Hospital and the Institute of Child Health, Multan, Pakistan.

I Sadaf Farooqi (IS)

Medical Research Council Metabolic Diseases Unit, Wellcome-MRC Institute of Metabolic Science - Metabolic Research Laboratories, University of Cambridge, Cambridge, UK.

Giles S H Yeo (GSH)

Medical Research Council Metabolic Diseases Unit, Wellcome-MRC Institute of Metabolic Science - Metabolic Research Laboratories, University of Cambridge, Cambridge, UK.

Stephen O'Rahilly (S)

Medical Research Council Metabolic Diseases Unit, Wellcome-MRC Institute of Metabolic Science - Metabolic Research Laboratories, University of Cambridge, Cambridge, UK.

Amélie Bonnefond (A)

Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK; INSERM UMR 1283, CNRS UMR 8199, European Genomic Institute for Diabetes (EGID), Institut Pasteur de Lille, Lille, France; University of Lille, Lille University Hospital, Lille, France.

Taeed A Butt (TA)

Department of Pediatrics, Fatima Memorial Hospital, Lahore, Pakistan.

Muhammad Arslan (M)

KAM School of Life Sciences, Forman Christian College, Lahore, Pakistan. Electronic address: muhammadarslan@fccollege.edu.pk.

Philippe Froguel (P)

Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK; INSERM UMR 1283, CNRS UMR 8199, European Genomic Institute for Diabetes (EGID), Institut Pasteur de Lille, Lille, France; University of Lille, Lille University Hospital, Lille, France. Electronic address: p.froguel@imperial.ac.uk.

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Enfant › High morbidity and mortality in children with...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › High morbidity and mortality in children with...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études transversales › High morbidity and mortality in children with...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Adipokines › Leptine › High morbidity and mortality in children with...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Collecte de données › Registre civil › Morbidité › High morbidity and mortality in children with...
questionsmedicales.fr › États, signes et symptômes pathologiques › Signes et symptômes › Obésité › Obésité morbide › High morbidity and mortality in children with...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Études rétrospectives › High morbidity and mortality in children with...