Clinical and Laboratory Characteristics of MODY Cases, Genetic Mutation Spectrum and Phenotype-genotype Relationship
Elif Özsu1, Semra Çetinkaya2, Semih Bolu3, Nihal Hatipoğlu4, Şenay Savaş Erdeve2, Olcay Evliyaoğlu5, Firdevs Baş6, Atilla Çayır7, Ismail Dündar8, Emine Demet Akbaş9, Seyit Ahmet Uçaktürk9, Merih Berberoğlu1, Zeynep Şıklar1, Şervan Özalkak2, Nursel Muratoğlu Şahin2, Melikşah Keskin2, Ülkü Gül Şiraz4, Hande Turan5, Ayşe Pınar Öztürk6, Eda Mengen10, Elif Sağsak11, Fatma Dursun12, Nesibe Akyürek13, Sevinç Odabaşı Güneş14, Zehra Aycan11Ankara University Faculty of Medicine, Department of Pediatric Endocrinology, Ankara, Turkey2Dr. Sami Ulus Obstetrics and Gynecology, Pediatric Health and Disease Training and Research Hospital, Clinic of Pediatric Endocrinology, Ankara, Turkey
3Adıyaman Training and Research Hospital, Clinic of Pediatric Endocrinology, Adıyaman, Turkey
4Erciyes University Faculty of Medicine, Department of Pediatric Endocrinology, Kayseri, Turkey
5İstanbul University Cerrahpaşa-Cerrahpaşa Faculty of Medicine, Department of Pediatric Endocrinology, İstanbul, Turkey
6İstanbul University, İstanbul Faculty of Medicine, Department of Pediatric Endocrinology, İstanbul, Turkey
7Erzurum Regional Training and Research Hospital, Clinic of Pediatric Endocrinology, Erzurum, Turkey
8Malatya Training and Research Hospital, Clinic of Pediatric Endocrinology, Malatya, Turkey
9Adana Training and Research Hospital, Clinic of Pediatric Endocrinology, Adana, Turkey
10Çukurova University Faculty of Medicine, Department of Pediatric Endocrinology, Adana, Turkey
11Yeditepe University Faculty of Medicine, Department of Pediatric Endocrinology İstanbul, Turkey
12Ümraniye Training and Research Hospital, Clinic of Pediatric Endocrinology, İstanbul, Turkey
13Başkent University, Konya Training and Research Hospital, Clinic of Pediatric Endocrinology, Konya, Turkey
14Gülhane Training and Research Hospital, Clinic of Pediatric Endocrinology, Ankara, Turkey
INTRODUCTION: 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.
DISCUSSION AND 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.
Manuscript Language: English
