Case Reports Journal Article Epublish 1 citation
PubMed: 42737637 DOI: 10.3390/ijms27177740
Setmelanotide Response Variability in Two Genetically Confirmed Pediatric Kidney Transplant Recipients with Bardet-Biedl Syndrome.
Int J Mol Sci 27(17)
Authors: Antonia Kondou, Pavlos Siolos, Georgia Sotiriou, Charalampos Agakidis, John Dotis, Athanasios Christoforidis, Nikoleta Printza
Affiliations
- Pediatric Nephrology Unit, First Department of Pediatrics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Hippokration General Hospital of Thessaloniki, 54642 Thessaloniki, Greece.
- First Department of Pediatrics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Hippokration General Hospital of Thessaloniki, 54642 Thessaloniki, Greece.
- Pediatric Endocrinology and Diabetes Mellitus Unit, First Department of Pediatrics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Hippokration General Hospital of Thessaloniki, 54642 Thessaloniki, Greece.
- Third Department of Pediatrics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Hippokration General Hospital of Thessaloniki, 54642 Thessaloniki, Greece.
Abstract
Bardet-Biedl syndrome (BBS) is a genetically heterogeneous ciliopathy associated with hyperphagic obesity and kidney disease. Evidence on setmelanotide after pediatric kidney transplantation is limited. We evaluated two children with BBS treated with setmelanotide after kidney transplantation, collecting anthropometric, hunger, metabolic, graft-function, cyclosporine and genetic data. Patient 1, a 17-year-old boy with a homozygous pathogenic SDCCAG8 exon deletion, improved over 12 months: weight 55.6 to 48.0 kg, BMI 26.6 to 23.0 kg/m 2, BMI-for-age z-score +1.60 to +0.43, maximal-hunger score 8/10 to 5/10, and HbA1c 6.5% to 5.1%. Patient 2, an 8-year-old girl with a homozygous likely pathogenic BBS5 splice-site variant and a heterozygous PCSK1 N221D variant, showed reduced hunger and an initial z-score fall from +6.10 to +5.69 by month 2.5, meeting the 0.2-point threshold for clinically meaningful change; this was not sustained, and BMI rose from 38.0 to 42.7 kg/m 2 by eight months despite a dose of 3 mg/day. Graft function and cyclosporine trough concentrations remained stable, and skin hyperpigmentation was the only treatment-related adverse effect. In these two patients, setmelanotide was not associated with graft deterioration or altered cyclosporine trough concentrations, although two cases cannot establish safety. The divergent trajectories highlight interindividual variability; the role of PCSK1 N221D remains uncertain, and these observations are hypothesis-generating.
MeSH
Hyperphagia, Ciliopathies, Pediatric Obesity, Kidney, Bardet-Biedl Syndrome, Cyclosporine, Transplants, Kidney Transplantation, Hunger, Transplantation