Diagnostic and therapeutic odyssey of two patients with compound heterozygous leptin receptor deficiency

Molecular and Cellular Pediatrics

Martin Wabitsch¹  Julia von Schnurbein¹  Stefanie Zorn¹  Katja Kohlsdorf¹  Christian Denzer¹ 

[1] Center for Rare Endocrine Diseases, Division of Paediatric Endocrinology and Diabetes, Department of Paediatrics and Adolescent Medicine, Ulm University Medical Centre, 89075, Ulm, Germany;

关键词: Leptin receptor;    Genetics;    Monogenetic obesity;    Early-onset obesity;    Hyperphagia;   

DOI  :  10.1186/s40348-020-00107-3

来源: Springer

【 摘 要 】

BackgroundRare genetic variations in the leptin-melanocortin signalling pathway can severely impair appetite regulation and cause extreme obesity in early childhood.Case presentationOur case reports describe the diagnostic and therapeutic procedures in a girl as well as in a non-related boy of non-consanguineous, German parents with severe early-onset obesity, pronounced hyperphagia, and permanent food-seeking behaviour. Excessive weight gain within the first year of life initiated extensive diagnostics without finding a causal diagnosis. Furthermore, a wide range of intensive, interdisciplinary, and behavioural therapies for weight control were unsuccessful. Prior to bariatric surgery, the 18-year-old girl and the 14-year-old boy reached a BMI of 67.7 kg/m2 and 55.2 kg/m2, respectively. However, even surgical outcomes were unsatisfactory. A subsequently initiated genetic analysis including sequencing of the leptin receptor gene revealed compound heterozygous variants as a cause of the severe early-onset obesity in both patients (c.2598-3_2607delTAGAATGAAAAAG and c.2227 T>C; c.1874G>A and c.2051A>C). Both patients were enrolled in the clinical study RM-493-015 and treated with melanocortin receptor agonist setmelanotide. Currently, they are still on setmelanotide treatment in the extension trial RM-493-022.ConclusionOur case report illustrates the urgent necessity of early genetic diagnostics in children with severe early-onset obesity to avoid frustrating and potentially damaging therapies. Thus, genetic examination should precede bariatric surgery. In the future, several pharmacological therapies will be available for some forms of monogenetic obesity.

【 授权许可】

CC BY