Academic Journal
Setmelanotide Response Variability in Two Genetically Confirmed Pediatric Kidney Transplant Recipients with Bardet-Biedl Syndrome.
| Τίτλος: | Setmelanotide Response Variability in Two Genetically Confirmed Pediatric Kidney Transplant Recipients with Bardet-Biedl Syndrome. |
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| Συγγραφείς: | Kondou A; 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., Siolos P; First Department of Pediatrics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Hippokration General Hospital of Thessaloniki, 54642 Thessaloniki, Greece., Sotiriou G; 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., Agakidis C; First Department of Pediatrics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Hippokration General Hospital of Thessaloniki, 54642 Thessaloniki, Greece., Dotis J; Third Department of Pediatrics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Hippokration General Hospital of Thessaloniki, 54642 Thessaloniki, Greece., Christoforidis A; 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., Printza N; 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. |
| Πηγή: | International journal of molecular sciences [Int J Mol Sci] 2026 Aug 29; Vol. 27 (17). Date of Electronic Publication: 2026 Aug 29. |
| Τύπος έκδοσης: | Case Reports; Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Basel, Switzerland : MDPI, [2000- |
| Ιατρικοί όροι (MeSH): | Bardet-Biedl Syndrome*/genetics , Bardet-Biedl Syndrome*/drug therapy , alpha-MSH*/analogs & derivatives , alpha-MSH*/therapeutic use , Kidney Transplantation*, Proprotein Convertase 1/genetics ; Humans ; Child ; Adolescent ; Female ; Male ; Transplant Recipients |
| Περίληψη: | 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/m2, 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/m2 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. |
| References: | Nat Med. 2018 May;24(5):551-555. (PMID: 29736023) Nat Genet. 2008 Aug;40(8):943-5. (PMID: 18604207) Eur J Hum Genet. 2024 Nov;32(11):1347-1360. (PMID: 39085583) Nat Genet. 2010 Oct;42(10):840-50. (PMID: 20835237) NPJ Genom Med. 2022 Jul 14;7(1):41. (PMID: 35835773) Nat Genet. 2020 Nov;52(11):1145-1150. (PMID: 33046855) Diabetes. 2012 Feb;61(2):383-90. (PMID: 22210313) Lancet Diabetes Endocrinol. 2022 Dec;10(12):859-868. (PMID: 36356613) Pediatr Nephrol. 2016 Nov;31(11):2153-61. (PMID: 27245600) Lancet Diabetes Endocrinol. 2020 Dec;8(12):960-970. (PMID: 33137293) Eur J Hum Genet. 2013 Jan;21(1):8-13. (PMID: 22713813) Lancet Diabetes Endocrinol. 2025 Jan;13(1):29-37. (PMID: 39549719) J Clin Invest. 2021 May 3;131(9):. (PMID: 33938449) Hum Mutat. 2019 Nov;40(11):2068-2087. (PMID: 31283077) Pediatr Nephrol. 2017 Aug;32(8):1443-1450. (PMID: 28361229) J Clin Invest. 2025 Apr 15;135(12):. (PMID: 40233116) Lancet Diabetes Endocrinol. 2024 Jun;12(6):380-389. (PMID: 38697184) N Engl J Med. 1989 Oct 12;321(15):1002-9. (PMID: 2779627) Nat Genet. 2018 Feb;50(2):180-185. (PMID: 29311635) PLoS Genet. 2016 Feb 29;12(2):e1005890. (PMID: 26926121) Hum Mol Genet. 2009 Apr 1;18(7):1323-31. (PMID: 19150989) |
| Contributed Indexing: | Keywords: BBS5; Bardet–Biedl syndrome; PCSK1; SDCCAG8; ciliopathy; hyperphagia; kidney transplantation; melanocortin-4 receptor; pediatric obesity; setmelanotide |
| Substance Nomenclature: | 581-05-5 (alpha-MSH) 0 (setmelanotide) EC 3.4.21.93 (Proprotein Convertase 1) EC 3.4.21.93 (PCSK1 protein, human) |
| Entry Date(s): | Date Created: 20260915 Date Completed: 20260915 Latest Revision: 20260923 |
| Update Code: | 20260924 |
| PubMed Central ID: | PMC13566516 |
| DOI: | 10.3390/ijms27177740 |
| PMID: | 42737637 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1422-0067 |
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| DOI: | 10.3390/ijms27177740 |