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Early childhood BMI trajectories in monogenic obesity due to leptin, leptin receptor, and melanocortin 4 receptor deficiency

International Journal of Obesity volume 42, pages 1602–1609 (2018)Cite this article

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Abstract

Objective:

To evaluate whether early childhood body mass index (BMI) is an appropriate indicator for monogenic obesity.

Methods:

A cohort of n = 21 children living in Germany or Austria with monogenic obesity due to congenital leptin deficiency (group LEP, n = 6), leptin receptor deficiency (group LEPR, n = 6) and primarily heterozygous MC4 receptor deficiency (group MC4R, n = 9) was analyzed. A control group (CTRL) was defined that consisted of n = 22 obese adolescents with no mutation in the above mentioned genes. Early childhood (0–5 years) BMI trajectories were compared between the groups at selected time points.

Results:

The LEP and LEPR group showed a tremendous increase in BMI during the first 2 years of life with all patients displaying a BMI >27 kg/m2 (27.2–38.4 kg/m2) and %BMIP95 (percentage of the 95th percentile BMI for age and sex) >140% (144.8–198.6%) at the age of 2 years and a BMI > 33 kg/m2 (33.3–45.9 kg/m2) and %BMIP95 > 184% (184.1–212.6%) at the age of 5 years. The MC4R and CTRL groups had a later onset of obesity with significantly lower BMI values at both time points (p < 0.01).

Conclusion:

As result of the investigation of early childhood BMI trajectories in this pediatric cohort with monogenic obesity we suggest that BMI values >27.0 kg/m2 or %BMIP95 > 140% at the age of 2 years and BMI values >33.0 kg/m2 or %BMIP95 > 184% at the age of 5 years may be useful cut points to identify children who should undergo genetic screening for monogenic obesity due to functionally relevant mutations in the leptin gene or leptin receptor gene.

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Acknowledgements

Funding

The study was funded by the German Ministry of Education and Research (BMBF) and is integrated in the Competence Network Obesity (FKZ 01GI1120A).

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Authors and Affiliations

  1. Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Eythstr. 24, D-89075, Ulm, Germany

    Katja Kohlsdorf, Adriana Nunziata, Jan-Bernd Funcke, Stephanie Brandt, Julia von Schnurbein, Heike Vollbach, Pamela Fischer-Posovszky & Martin Wabitsch

  2. Division of Endocrinology, Boston Children’s Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA

    Belinda Lennerz

  3. Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Währinger Gürtel 18-20, A-1090, Wien, Austria

    Maria Fritsch & Susanne Greber-Platzer

  4. Department of Pediatrics, Division of General Pediatrics, Medical University of Graz, Auenbruggerplatz 34/2, A-8036, Graz, Austria

    Elke Fröhlich-Reiterer

  5. Institute of Human Genetics, University of Ulm, Albert-Einstein-Alee 11, D-89075, Ulm, Germany

    Manuel Luedeke & Guntram Borck

  6. Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Eythstr. 24, D-89, Ulm, Germany

    Klaus-Michael Debatin

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Correspondence to Martin Wabitsch.

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Kohlsdorf, K., Nunziata, A., Funcke, JB. et al. Early childhood BMI trajectories in monogenic obesity due to leptin, leptin receptor, and melanocortin 4 receptor deficiency. Int J Obes 42, 1602–1609 (2018). https://doi.org/10.1038/s41366-018-0049-6

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