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.
KAM School of Life Sciences, Forman Christian College, Lahore, Pakistan.
Cell Rep Med. 2023 Sep 19;4(9):101187. doi: 10.1016/j.xcrm.2023.101187. Epub 2023 Sep 1.
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.
瘦素信号缺陷导致的重度肥胖的长期临床结局尚不清楚。我们对一大群瘦素（LEP）、LEP 受体（LEPR）或黑素皮质素 4 受体（MC4R）缺陷的儿童（n=145）进行了回顾性横断面研究，以评估疾病的进展情况。受影响的个体接受身体、临床和代谢评估。我们报告称，LEP（26%）或 LEPR 缺乏症（9%）患儿死亡率非常高，主要是由于严重的肺部和胃肠道感染。此外，40%的 LEP 或 LEPR 缺乏症幸存儿童会经历危及生命的肺部或胃肠道感染发作。尽管目前有针对 LEP 和 LEPR 缺乏症的精准药物，但在巴基斯坦尚未获得这些药物。对 LEP 或 LEPR 缺乏症对发病率和早期死亡率、受教育程度以及随之而来的污名化的严重影响的认识，应促使人们紧急向这些儿童提供现有的救命药物。
