Clinical and Laboratory Characteristics of MODY Cases, Genetic Mutation Spectrum and Phenotype-genotype Relationship

Autor: Özsu E; Ankara University Faculty of Medicine, Department of Pediatric Endocrinology, Ankara, Turkey, Çetinkaya S; Dr. Sami Ulus Obstetrics and Gynecology, Pediatric Health and Disease Training and Research Hospital, Clinic of Pediatric Endocrinology, Ankara, Turkey, Bolu S; Adıyaman Training and Research Hospital, Clinic of Pediatric Endocrinology, Adıyaman, Turkey, Hatipoğlu N; Erciyes University Faculty of Medicine, Department of Pediatric Endocrinology, Kayseri, Turkey, Savaş Erdeve Ş; Dr. Sami Ulus Obstetrics and Gynecology, Pediatric Health and Disease Training and Research Hospital, Clinic of Pediatric Endocrinology, Ankara, Turkey, Evliyaoğlu O; İstanbul University Cerrahpaşa-Cerrahpaşa Faculty of Medicine, Department of Pediatric Endocrinology, İstanbul, Turkey, Baş F; İstanbul University, İstanbul Faculty of Medicine, Department of Pediatric Endocrinology, İstanbul, Turkey, Çayır A; Erzurum Regional Training and Research Hospital, Clinic of Pediatric Endocrinology, Erzurum, Turkey, Dündar İ; Malatya Training and Research Hospital, Clinic of Pediatric Endocrinology, Malatya, Turkey, Akbaş ED; Adana Training and Research Hospital, Clinic of Pediatric Endocrinology, Adana, Turkey, Uçaktürk SA; Adana Training and Research Hospital, Clinic of Pediatric Endocrinology, Adana, Turkey, Berberoğlu M; Ankara University Faculty of Medicine, Department of Pediatric Endocrinology, Ankara, Turkey, Şıklar Z; Ankara University Faculty of Medicine, Department of Pediatric Endocrinology, Ankara, Turkey, Özalkak Ş; Dr. Sami Ulus Obstetrics and Gynecology, Pediatric Health and Disease Training and Research Hospital, Clinic of Pediatric Endocrinology, Ankara, Turkey, Muratoğlu Şahin N; Dr. Sami Ulus Obstetrics and Gynecology, Pediatric Health and Disease Training and Research Hospital, Clinic of Pediatric Endocrinology, Ankara, Turkey, Keskin M; Dr. Sami Ulus Obstetrics and Gynecology, Pediatric Health and Disease Training and Research Hospital, Clinic of Pediatric Endocrinology, Ankara, Turkey, Şiraz ÜG; Erciyes University Faculty of Medicine, Department of Pediatric Endocrinology, Kayseri, Turkey, Turan H; İstanbul University Cerrahpaşa-Cerrahpaşa Faculty of Medicine, Department of Pediatric Endocrinology, İstanbul, Turkey, Öztürk AP; İstanbul University, İstanbul Faculty of Medicine, Department of Pediatric Endocrinology, İstanbul, Turkey, Mengen E; Çukurova University Faculty of Medicine, Department of Pediatric Endocrinology, Adana, Turkey, Sağsak E; Yeditepe University Faculty of Medicine, Department of Pediatric Endocrinology İstanbul, Turkey, Dursun F; Ümraniye Training and Research Hospital, Clinic of Pediatric Endocrinology, İstanbul, Turkey, Akyürek N; Başkent University, Konya Training and Research Hospital, Clinic of Pediatric Endocrinology, Konya, Turkey, Odabaşı Güneş S; Gülhane Training and Research Hospital, Clinic of Pediatric Endocrinology, Ankara, Turkey, Aycan Z; Ankara University Faculty of Medicine, Department of Pediatric Endocrinology, Ankara, Turkey
Jazyk: angličtina
Zdroj: Journal of clinical research in pediatric endocrinology [J Clin Res Pediatr Endocrinol] 2024 Sep 05; Vol. 16 (3), pp. 297-305. Date of Electronic Publication: 2024 Apr 26.
DOI: 10.4274/jcrpe.galenos.2024.2023-10-16
Abstrakt: Objective: Maturity onset diabetes of the young (MODY) occurs due to mutations in genes involved in pancreatic beta cell function and insulin secretion, has heterogeneous clinical and laboratory features, and account for 1-5% of all diabetes cases. The prevalence and distribution of MODY subtypes vary between countries. The aim of this study was to evaluate the clinical and laboratory characteristics, mutation distribution, and phenotype-genotype relationship in a large case series of pediatric Turkish patients genetically diagnosed with MODY.
Methods: MODY cases from 14 different pediatric endocrinology departments were included. Diagnosis, treatment, follow-up data, and results of genetic analysis were evaluated.
Results: A total of 224 patients were included, of whom 101 (45%) were female, and the mean age at diagnosis was 9.4±4.1 years. Gene variant distribution was: 146 (65%) GCK; 43 (19%) HNF1A ; 8 (3.6%) HNF4A , 8 (3.6%) KLF11 and 7 (3.1%) HNF1B . The remaining 12 variants were: PDX (n=1), NEUROD1 (n=3), CEL (n=1), INS (n=3), ABCC8 (n= 3) and KJNC11 (n=1). Of the cases, 197 (87.9%) were diagnosed with incidental hyperglycemia, 16 with ketosis (7%) and 7 (3%) with diabetic ketoacidosis (DKA), while 30% presented with classical symptoms of diabetes. Two-hundred (89%) had a family history of diabetes. Anti-GAD antibody was detected in 13 cases, anti-islet antibody in eight and anti-insulin antibody in four. Obesity was present in 16. Distribution of therapy was: 158 (71%) diet only; 23 (11%) intensive insulin treatment; 17 (7.6%) sulfonylureas; 10 (4.5%) metformin; and 6 (2.7%) insulin and oral anti-diabetic treatment.
Conclusion: This was the largest genetically diagnosed series from Turkey. The most common gene variants were GCK and HNF1A with much lower proportions for other MODY types. Hyperglycemia was the most common presenting symptom while 11% of patients had diabetes-associated autoantibodies and 7% were obese. The majority of patients received dietary management only.
Competing Interests: Conflict of interest: None declared.
(©Copyright 2024 by Turkish Society for Pediatric Endocrinology and Diabetes / The Journal of Clinical Research in Pediatric Endocrinology published by Galenos Publishing House.)
Databáze: MEDLINE
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