PURPOSE: In patients diagnosed with diabetes mellitus (DM) before the age of 12 months, there is an increasing recognition of diabetes caused by single-gene mutations, also known as monogenic diabetes of infancy or neonatal DM (NDM). This study aimed to classify patients at Alexandria University Children's Hospital (AUCH) diagnosed with infantile-onset DM into type 1 DM (T1DM) or NDM and to detect differences in molecular characteristics of NDM patients at our center in comparison to other countries. METHODS: This retrospective/prospective observational study was conducted on 39 patients diagnosed with infantile-onset DM (age of onset ≤1 year) at AUCH from January 2003 to November 2020. The patients were divided into 2 groups according to age at the onset of DM: ≤6 months and >6-12 months. Molecular testing was done in patients diagnosed with DM at ≤6 months and those with negative autoantibodies. RESULTS: Twelve patients were diagnosed with DM at age ≤6 months and 27 patients were diagnosed between 6-12 months. Seventeen patients (43.6%) had T1DM, whereas 9 patients (23.1%) had genetically confirmed NDM, including 3 harboring novel mutations. The most common genetic causes of NDM were EIF2AK3 mutations (n=3), followed by KCNJ11 (n=2) and ABCC8 (n=2). Other mutations included SLC19A2 (n=1) and INS (n=1). Three patients with potassium ATP channel mutations were transferred from insulin to sulfonylurea treatment. CONCLUSION: It is essential to identify patients with NDM clinically and confirm the diagnosis by molecular testing to distinguish them from T1DM as it helps in refining their management, predicting prognosis, and guiding genetic counseling.
PURPOSE: In patients diagnosed with diabetes mellitus (DM) before the age of 12 months, there is an increasing recognition of diabetes caused by single-gene mutations, also known as monogenic diabetes of infancy or neonatal DM (NDM). This study aimed to classify patients at Alexandria University Children's Hospital (AUCH) diagnosed with infantile-onset DM into type 1 DM (T1DM) or NDM and to detect differences in molecular characteristics of NDM patients at our center in comparison to other countries. METHODS: This retrospective/prospective observational study was conducted on 39 patients diagnosed with infantile-onset DM (age of onset ≤1 year) at AUCH from January 2003 to November 2020. The patients were divided into 2 groups according to age at the onset of DM: ≤6 months and >6-12 months. Molecular testing was done in patients diagnosed with DM at ≤6 months and those with negative autoantibodies. RESULTS: Twelve patients were diagnosed with DM at age ≤6 months and 27 patients were diagnosed between 6-12 months. Seventeen patients (43.6%) had T1DM, whereas 9 patients (23.1%) had genetically confirmed NDM, including 3 harboring novel mutations. The most common genetic causes of NDM were EIF2AK3 mutations (n=3), followed by KCNJ11 (n=2) and ABCC8 (n=2). Other mutations included SLC19A2 (n=1) and INS (n=1). Three patients with potassium ATP channel mutations were transferred from insulin to sulfonylurea treatment. CONCLUSION: It is essential to identify patients with NDM clinically and confirm the diagnosis by molecular testing to distinguish them from T1DM as it helps in refining their management, predicting prognosis, and guiding genetic counseling.
Entities:
Keywords:
Infantile-onset diabetes; Monogenic diabetes of infancy; Neonatal diabetes mellitus; Potassium ATP channel; Sulfonylurea; Wolcott-Rallison syndrome
Authors: D Iafusco; M A Stazi; R Cotichini; M Cotellessa; M E Martinucci; M Mazzella; V Cherubini; F Barbetti; M Martinetti; F Cerutti; F Prisco Journal: Diabetologia Date: 2002-05-03 Impact factor: 10.122
Authors: Mousa A Abujbara; Mohammed I Liswi; Mohammed S El-Khateeb; Sarah E Flanagan; Sian Ellard; Kamel M Ajlouni Journal: J Pediatr Endocrinol Metab Date: 2014-09 Impact factor: 1.634
Authors: Elizabeth J Mayer-Davis; Anna R Kahkoska; Craig Jefferies; Dana Dabelea; Naby Balde; Chun X Gong; Pablo Aschner; Maria E Craig Journal: Pediatr Diabetes Date: 2018-10 Impact factor: 4.866
Authors: Sue Richards; Nazneen Aziz; Sherri Bale; David Bick; Soma Das; Julie Gastier-Foster; Wayne W Grody; Madhuri Hegde; Elaine Lyon; Elaine Spector; Karl Voelkerding; Heidi L Rehm Journal: Genet Med Date: 2015-03-05 Impact factor: 8.822
Authors: Abdelhadi M Habeb; Asma Deeb; Matthew Johnson; Mohammed Abdullah; Majidah Abdulrasoul; Hussain Al-Awneh; Mohammed S F Al-Maghamsi; Fathiya Al-Murshedi; Ramlah Al-Saif; Siham Al-Sinani; Dina Ramadan; Hala Tfayli; Sarah E Flanagan; Sian Ellard Journal: Horm Res Paediatr Date: 2015-02-05 Impact factor: 2.852
Authors: Huseyin Demirbilek; Ved Bhushan Arya; Mehmet Nuri Ozbek; Jayne A L Houghton; Riza Taner Baran; Melek Akar; Selahattin Tekes; Heybet Tuzun; Deborah J Mackay; Sarah E Flanagan; Andrew T Hattersley; Sian Ellard; Khalid Hussain Journal: Eur J Endocrinol Date: 2015-03-09 Impact factor: 6.664
Authors: Lisa R Letourneau; David Carmody; Kristen Wroblewski; Anna M Denson; May Sanyoura; Rochelle N Naylor; Louis H Philipson; Siri Atma W Greeley Journal: Diabetes Care Date: 2017-08-04 Impact factor: 19.112
Authors: M N Weedon; A T Hattersley; K A Patel; R A Oram; S E Flanagan; E De Franco; K Colclough; M Shepherd; S Ellard Journal: Diabetes Date: 2016-04-05 Impact factor: 9.461
Authors: Matthew B Johnson; Kashyap A Patel; Elisa De Franco; William Hagopian; Michael Killian; Timothy J McDonald; Timothy I M Tree; Clara Domingo-Vila; Michelle Hudson; Suzanne Hammersley; Rebecca Dobbs; Sian Ellard; Sarah E Flanagan; Andrew T Hattersley; Richard A Oram Journal: Diabetologia Date: 2020-10-08 Impact factor: 10.122