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. 2023 Sep 19;4(9):101187.
doi: 10.1016/j.xcrm.2023.101187. Epub 2023 Sep 1.

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

Sadia Saeed  1 , Roohia Khanam  2 , Qasim M Janjua  3 , Jaida Manzoor  4 , Lijiao Ning  5 , Sharoon Hanook  6 , Mickaël Canouil  5 , Muhammad Ali  7 , Hina Ayesha  8 , Waqas I Khan  9 , I Sadaf Farooqi  10 , Giles S H Yeo  10 , Stephen O'Rahilly  10 , Amélie Bonnefond  11 , Taeed A Butt  12 , Muhammad Arslan  13 , Philippe Froguel  14
Affiliations

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

Sadia Saeed et al. Cell Rep Med. .

Abstract

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.

Keywords: age-related changes; body growth; consanguinity; leptin-signaling deficiency; metabolism; monogenic obesity; morbidity; mortality; oxidative stress.

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Conflict of interest statement

Declaration of interests The authors declare no competing interests.

Figures

None
Graphical abstract
Figure 1
Figure 1
Radar chart representing the severity of the obesity-associated risks in children with LEP or LEPR deficiency compared with those with MC4R deficiency
Figure 2
Figure 2
Survival curve of children with LEP, LEPR, and MC4R deficiencies and severely obese children negative for mutations in known obesity genes (obese controls) Kaplan-Meier group log-rank p < 0.05.
See this image and copyright information in PMC

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