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One-year metreleptin in Colombian sisters with congenital leptin deficiency
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Autores
Bastarrachea, Raul A.
Arango, Carlos
Rodriguez-Ayala, Ernesto
Laviada-Molina, Hugo A.
Licinio, Julio
Hernandez-Escalante, Victor M.
Neri Morales, Constanza
Celis-Regalado, Luis G.
Nava-Gonzalez, Edna J.
Gonzalez, Adriana
Fecha
2025-01-01
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Taylor & Francis
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Resumen
Abstract
We discovered two adult sisters in Colombia, lineally consanguineous, with severe obesity andundetectable serum leptin levels despite markedly elevated body fat. Their clinical profileincluded childhood-onset extreme weight gain, intense hunger, hyperphagia, hypogonadotropichypogonadism, and family history of obesity. Direct sequencing of the LEP gene revealed a novelhomozygous missense mutation in exon 3 (c.350G>T [p.C117F]). The presence of this mutation,undetectable leptin, and severe obesity confirmed a diagnosis of monogenic leptin deficiency.Here we describe the clinical outcomes of a 12-month treatment with recombinant human leptin(metreleptin). Metabolic and endocrine assessments were conducted before and after therapy.Metreleptin therapy significantly reduced BMI: from 59 to 38 kg/m2 (OBX1, age 27) and 60 to 48kg/m2 (OBX2, age 24). Total body fat mass decreased, serum lipids normalized, and insulinsensitivity improved. Hypogonadotropic hypogonadism reversed, and menstruation resumed.Thus, metreleptin reversed the major metabolic and endocrine abnormalities associated withleptin deficiency in these sisters. Limitations include the small sample size, absence of a controlgroup, and lack of anti-metreleptin antibody measurements. Nevertheless, our findings supportthat leptin replacement with metreleptin is currently the only effective hormonal treatment forthis monogenic form of human obesity.
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Keywords
Congenital leptin deficiency , Colombian sisters , LEP gene , recombinant human leptin(metreleptin) , leptin replacement therapy
