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

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 in-fections. In addition, 40% of surviving children with LEP or LEPR deficiency experience life-threatening ep-isodes 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 stigma-tization should spur efforts to deliver the available life-saving drugs to these children as a matter of urgency.

Automated summary

This study investigated the impact of leptin or leptin receptor deficiency on morbidity, early mortality, and educational attainment in a large cohort of affected children. It found that these deficiencies had a severe impact on the affected individuals, with high mortality rates and life-threatening episodes of lung or gastrointestinal infections.