A National Multicenter Study of Leptin and Leptin Receptor Deficiency and Systematic Review
Authors' conclusion
Frameshift variants were more common in patients with LEP deficiency whereas missense variants were more common in LEPR deficiency. Patients with LEP deficiency were identified at younger ages, had higher BMI SD scores, and had higher rates of hyperinsulinemia than patients with LEPR deficiency. Eleven patients benefitted from long-term metreleptin, with 1 losing efficacy due to neutralizing antibodies.
Study context
- Population
- Patients with homozygous leptin (LEP) or leptin receptor (LEPR) variants (childhood-onset obesity); national cohort plus cases from the literaturecohort
- Participants
- 18 patients
- Comparison
- LEP deficiency vs LEPR deficiency
- LEPn = 11
- LEPRn = 7reference
- Outcome
- Genotype-phenotype relationships (152 patients incl. 134 from literature)
Methodological detailsnational, systematic literature review (July 2022)
- National
- Systematic literature review (July 2022)
Pooled result
As reported in the abstract
- Most common variant type in LEP: frameshift
- 48%
- Most common variant type in LEPR: missense
- 35%
- Higher body mass index (BMI) SD score more closely associated with frameshift variants
- P = .02
Further pooled results
New cases: novel pathogenic variants
- Novel pathogenic variants among 10 new cases: LEP c.16delC and LEPR c.40 + 5G > C
- 2
Metreleptin treatment in LEP deficiency
- Patients with LEP deficiency receiving metreleptin
- 11
- Treated for over 20 years
- 4
Safety
Loss of metreleptin efficacy
- Loss of efficacy associated with neutralizing antibody development
- 1 patient
Original publication
A National Multicenter Study of Leptin and Leptin Receptor Deficiency and Systematic Review. J Clin Endocrinol Metab. Published 24 February 2023. doi:10.
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