ESPE Abstracts (2015) 84 P-2-333

Leptin Replacement Improves Central Ventilation in a Patient with Congenital Leptin Deficiency: First Report in Childhood

Laura Lucaccionia, Philip L Daviesb, Neil A Gibsonb, Sadaf Farooqic & M Guftar Shaikha


aDevelopmental Endocrinology Research Group, Royal Hospital for Sick Children, University of Glasgow, Glasgow, UK; bRespiratory Department, Royal Hospital for Sick Children, Glasgow, UK; cMRC Metabolic Diseases Unit, Metabolic Research Laboratories, Wellcome Trust–MRC Institute of Metabolic Science, NIHR Cambridge Biomedical Research Centre, Addenbrooke’s Hospital, University of Cambridge, Cambridge, UK


Background: Congenital leptin deficiency (CLD) is characterized by severe early-onset obesity due to hyperphagia and impaired satiety. The impact of obesity in obstructive sleep apnoea hypopnoea syndrome (OSAHS) was originally reported as mechanical, but recent data suggest that adipokines may influence central ventilation. We highlight that treatment with recombinant human leptin (RHL) in CLD with OSAHS improves ventilation before weight loss.

Case presentation: A 10-month-old female of Pakistani origin was severely obese (weight: 17.9 kg (+5.6 SDS) and BMI: 29.4 kg/m2 (+5.3 SDS)). Born at term to consanguineous parents. Mother reported rapid weight gain during first months of life, due to intense hyperphagia with food-seeking behaviour. Family history showed a first cousin with CLD: genetic analysis confirmed the same homozygous leptin mutation. RHL replacement was started with good reduction of appetite. Three months before starting treatment (weight: 26.1 kg (+7.6 SDS)) oxicapnography showed normal mean saturations and CO2 but clusters of deep desaturations (desaturation index (DI) 19.8/h of >4%). After 50 days of treatment polysomnography was performed showing a significant improvement in clusters of desaturation (DI 9.3/h) and a mixed pattern of both obstructive and central events with an apnoea hypopnoea index (AHI) 13.7/h. At this stage the weight was stable at 26.9 kg (+6.7 SDS), BMI was 34.8 kg/m2 (+6.6 SDS). After 5 months of treatment a significant loss of weight was seen (weight: 22.0 kg and BMI: 32.6 kg/m2, both at +4.7 SDS). Repeat polysomnography showed marked improvement with an AHI 4/h and a DI 4.2/h.

Conclusion: To the best of our knowledge, this is the first report showing an improvement in ventilation, in a patient with CLD following treatment with RHL before significant weight loss. In mice, leptin microinjections into specific brain areas, are associated with increased pulmonary ventilation and enhanced bioelectrical activity of inspiratory muscles, suggesting that leptin may influence ventilation through a direct effect on respiratory control centres. Leptin appears to have central effects on ventilatory regulation, which need to be explored further.

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