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

Int J Obes (Lond). 2018 Sep;42(9):1602-1609. doi: 10.1038/s41366-018-0049-6. Epub 2018 Feb 27.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Austria / epidemiology
  • Body Mass Index*
  • Child
  • Child, Preschool
  • Female
  • Germany / epidemiology
  • Humans
  • Leptin / deficiency*
  • Leptin / genetics
  • Male
  • Pediatric Obesity / epidemiology*
  • Pediatric Obesity / genetics*
  • Receptor, Melanocortin, Type 4 / deficiency*
  • Receptor, Melanocortin, Type 4 / genetics
  • Receptors, Leptin / deficiency*
  • Receptors, Leptin / genetics
  • Retrospective Studies
  • Young Adult

Substances

  • LEP protein, human
  • LEPR protein, human
  • Leptin
  • MC4R protein, human
  • Receptor, Melanocortin, Type 4
  • Receptors, Leptin