Clinical and genetic heterogeneity of HNF4A/HNF1A mutations in a multicentre paediatric cohort with hyperinsulinaemic hypoglycaemia
| العنوان: | Clinical and genetic heterogeneity of HNF4A/HNF1A mutations in a multicentre paediatric cohort with hyperinsulinaemic hypoglycaemia |
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| المؤلفون: | Sinéad M McGlacken-Byrne, Jasmina Kallefullah Mohammad, Niamh Conlon, Diliara Gubaeva, Julie Siersbæk, Anders Jørgen Schou, Huseyin Demirbilek, Antonia Dastamani, Jayne A L Houghton, Klaus Brusgaard, Maria Melikyan, Henrik Christesen, Sarah E Flanagan, Nuala P Murphy, Pratik Shah |
| المصدر: | McGlacken-Byrne, S M, Mohammad, J K, Conlon, N, Gubaeva, D, Siersbæk, J, Schou, A J, Demirbilek, H, Dastamani, A, Houghton, J A L, Brusgaard, K, Melikyan, M, Christesen, H, Flanagan, S E, Murphy, N P & Shah, P 2022, ' Clinical and genetic heterogeneity of HNF4A/HNF1A mutations in a multicentre paediatric cohort with hyperinsulinaemic hypoglycaemia ', European Journal of Endocrinology, vol. 186, no. 4, pp. 417-427 . https://doi.org/10.1530/EJE-21-0897 |
| بيانات النشر: | Oxford University Press (OUP), 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Male, Adolescent, Endocrinology, Diabetes and Metabolism, Cohort Studies, Genetic Heterogeneity, Endocrinology, Hyperinsulinism, Diabetes Mellitus, Type 1/genetics, Birth Weight, Humans, Hepatocyte Nuclear Factor 1-alpha, Hepatocyte Nuclear Factor 1-alpha/genetics, Child, Medical History Taking, Diazoxide/therapeutic use, Hyperinsulinism/drug therapy, Diazoxide, Infant, Newborn, Infant, General Medicine, Fanconi Syndrome, Hypoglycemia, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Hepatocyte Nuclear Factor 4, Hepatocyte Nuclear Factor 4/genetics, Child, Preschool, Mutation, Diabetes Mellitus, Type 2/genetics, Hypoglycemia/drug therapy, Female, Fanconi Syndrome/genetics |
| الوصف: | Objective The phenotype mediated by HNF4A/HNF1A mutations is variable and includes diazoxide-responsive hyperinsulinaemic hypoglycaemia (HH) and maturity-onset diabetes of the young (MODY). Design We characterised an international multicentre paediatric cohort of patients with HNF4Aor HNF1Amutations presenting with HH over a 25-year period (1995–2020). Methods Clinical and genetic analysis data from five centres were obtained. Diazoxide responsiveness was defined as the ability to maintain normoglycaemia without intravenous glucose. Macrosomia was defined as a birth weight ≥90th centile. SPSS v.27.1 was used for data analysis. Results A total of 34 patients (70.6% female, n = 24) with a mean age of 7.1 years (s.d. 6.4) were included. A total of 21 different heterozygous HNF4Amutations were identified in 29 patients (four novels). Four different previously described heterozygous HNF1A mutations were detected in five patients. Most (97.1%, n = 33) developed hypoglycaemia by day 2 of life. The mean birth weight was 3.8 kg (s.d. 0.8), with most infants macrosomic (n = 21, 61.8%). Diazoxide was commenced in 28 patients (82.3%); all responded. HH resolved in 20 patients (58.8%) following a median of 0.9 years (interquartile range (IQR): 0.2–6.8). Nine patients (n = 9, 26.5%) had developmental delay. Two patients developed Fanconi syndrome (p.Arg63Trp, HNF4A) and four had other renal or hepatic findings. Five (14.7%) developed MODY at a median of 11.0 years (IQR: 9.0–13.9). Of patients with inherited mutations (n = 25, 73.5%), a family history of diabetes was present in 22 (88.0%). Conclusions We build on the knowledge of the natural history and pancreatic and extra-pancreatic phenotypes of HNF4A/HNF1Amutations and illustrate the heterogeneity of this condition. |
| تدمد: | 1479-683X 0804-4643 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f6c633e75590c4bd7905fb8beb09f440 https://doi.org/10.1530/eje-21-0897 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....f6c633e75590c4bd7905fb8beb09f440 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1479683X 08044643 |
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