Severe Early-Onset Obesity Due to Bioinactive Leptin Caused by a p.N103K Mutation in the Leptin Gene.

Abstract

CONTEXT:

Congenital leptin deficiency is a very rare cause of severe early-onset obesity. We recently characterized a mutation in the leptin gene (p.D100Y), which was associated with detectable leptin levels and bioinactivity of the hormone.

CASE DESCRIPTION:

We now describe two siblings, a 9-year-old girl and a 6-year-old boy with severe early-onset obesity and hyperphagia, both homozygous for a c.309C>A substitution in the leptin gene leading to a p.N103K amino acid exchange in the protein and detectable circulating levels of leptin. In vitro experiments in a heterologous cell system demonstrated that the mutated protein was biologically inactive. Treatment with sc recombinant human leptin led to rapid improvement of eating behavior and weight loss.

CONCLUSIONS:

Sequencing of the leptin gene may need to be considered in hyperphagic, severely obese children with detectable levels of circulating leptin.

• Authors: Martin Wabitsch, Jan-Bernd Funcke, Julia von Schnurbein, Friederike Denzer, Georgia Lahr, Inas Mazen, Mona El-Gammal, Christian Denzer, Anja Moss, Klaus-Michael Debatin, Peter Gierschik, Vanisha Mistry, Julia M Keogh, I Sadaf Farooqi, Barbara Moepps, Pamela Fischer-Posovszky
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 100 Issue 9 Pg. 3227-30 (Sep 2015) ISSN: 1945-7197 [Electronic] United States
• PMID: 26186301 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Leptin

Topics

• Body Weight (genetics)
• Child
• Female
• Humans
• Hyperphagia (genetics)
• Leptin (blood, genetics)
• Male
• Mutation
• Obesity (genetics)