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Journal of Pediatric Endocrinology and Metabolism

Editor-in-Chief: Kiess, Wieland

Ed. by Bereket, Abdullah / Darendeliler, Feyza / Dattani, Mehul / Gustafsson, Jan / Luo, Fei Hong / Toppari, Jorma / Turan, Serap Demircioglu

IMPACT FACTOR 2018: 1.239

CiteScore 2018: 1.22

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Volume 28, Issue 3-4


Maturity-onset diabetes of the young (MODY): an update

Ahmet Anık / Gönül Çatlı / Ayhan Abacı / Ece Böber
Published Online: 2015-01-10 | DOI: https://doi.org/10.1515/jpem-2014-0384


Maturity-onset diabetes of the young (MODY) is a group of monogenic disorders characterized by autosomal dominantly inherited non-insulin dependent form of diabetes classically presenting in adolescence or young adults before the age of 25 years. MODY is a rare cause of diabetes (1% of all cases) and is frequently misdiagnosed as Type 1 diabetes (T1DM) or Type 2 diabetes (T2DM). A precise molecular diagnosis is essential because it leads to optimal treatment of the patients and allows early diagnosis for their asymptomatic family members. Mutations in the glucokinase (GCK) (MODY 2) and hepatocyte nuclear factor (HNF)1A/4A (MODY 3 and MODY 1) genes are the most common causes of MODY. GCK mutations cause a mild, asymptomatic, and stable fasting hyperglycemia usually requiring no specific treatment. However, mutations in the HNF1A and HNF4A cause a progressive pancreatic β-cell dysfunction and hyperglycemia that can result in microvascular complications. Sulfonylureas are effective in these patients by acting on adenosine triphosphate (ATP)-sensitive potassium channels, although insulin therapy may be required later in life. Mutations in the HNF1B (MODY 5) is associated with pancreatic agenesis, renal abnormalities, genital tract malformations, and liver dysfunction. Compared to MODY 1, 2, 3, and 5, the remaining subtypes of MODY have a much lower prevalence. In this review, we summarize the main clinical and laboratory characteristics of the common and rarer causes of MODY.

Keywords: children; hyperglycemia; maturity-onset diabetes of the young; pancreatic β-cell


  • 1.

    Fajans SS, Bell GI. MODY: history, genetics, pathophysiology, and clinical decision making. Diabetes Care 2011;34:1878–84.CrossrefGoogle Scholar

  • 2.

    Osbak KK, Colclough K, Saint-Martin C, Beer NL, Bellanne-Chantelot C, et al. Update on mutations in glucokinase (GCK), which cause maturity-onset diabetes of the young, permanent neonatal diabetes, and hyperinsulinemic hypoglycemia. Hum Mutat 2009;30:1512–26.CrossrefGoogle Scholar

  • 3.

    McDonald TJ, Colclough K, Brown R, Shields B, Shepherd M, et al. Islet autoantibodies can discriminate maturity-onset diabetes of the young (MODY) from Type 1 diabetes. Diabet Med 2011;28:1028–33.Google Scholar

  • 4.

    Owen KR, Roland J, Smith K, Hattersley AT. Adolescent onset Type 2 diabetes in a non-obese Caucasian patient with an unbalanced translocation. Diabet Med 2003;20:483–5.CrossrefGoogle Scholar

  • 5.

    Tattersall RB. Mild familial diabetes with dominant inheritance. Q J Med 1974;43:339–57.Google Scholar

  • 6.

    Tattersall RB, Fajans SS. A difference between the inheritance of classical juvenile-onset and maturity-onset type diabetes of young people. Diabetes 1975;24:44–53.CrossrefGoogle Scholar

  • 7.

    Thanabalasingham G, Owen KR. Diagnosis and management of maturity onset diabetes of the young (MODY). Brit Med J 2011;343:d6044.CrossrefGoogle Scholar

  • 8.

    Ledermann HM. Maturity-onset diabetes of the young (MODY) at least ten times more common in Europe than previously assumed? Diabetologia 1995;38:1482.Google Scholar

  • 9.

    Shields BM, Hicks S, Shepherd MH, Colclough K, Hattersley AT, et al. Maturity-onset diabetes of the young (MODY): how many cases are we missing? Diabetologia 2010;53:2504–8.CrossrefGoogle Scholar

  • 10.

    Kropff J, Selwood MP, McCarthy MI, Farmer AJ, Owen KR. Prevalence of monogenic diabetes in young adults: a community-based, cross-sectional study in Oxfordshire, UK. Diabetologia 2011;54:1261–3.CrossrefGoogle Scholar

  • 11.

    Pihoker C, Gilliam LK, Ellard S, Dabelea D, Davis C, et al. Prevalence, characteristics and clinical diagnosis of maturity onset diabetes of the young due to mutations in HNF1A, HNF4A, and glucokinase: results from the SEARCH for Diabetes in Youth. J Clin Endocrinol Metab 2013;98:4055–62.CrossrefGoogle Scholar

  • 12.

    Thanabalasingham G, Pal A, Selwood MP, Dudley C, Fisher K, et al. Systematic assessment of etiology in adults with a clinical diagnosis of young-onset Type 2 diabetes is a successful strategy for identifying maturity-onset diabetes of the young. Diabetes Care 2012;35:1206–12.CrossrefGoogle Scholar

  • 13.

    Kavvoura FK, Owen KR. Maturity onset diabetes of the young: clinical characteristics, diagnosis and management. Pediatr Endocrinol Rev 2012;10:234–42.Google Scholar

  • 14.

    Plengvidhya N, Kooptiwut S, Songtawee N, Doi A, Furuta H, et al. PAX4 mutations in Thais with maturity onset diabetes of the young. J Clin Endocrinol Metab 2007;92:2821–6.CrossrefGoogle Scholar

  • 15.

    Molven A, Ringdal M, Nordbo AM, Raeder H, Stoy J, et al. Mutations in the insulin gene can cause MODY and autoantibody-negative Type 1 diabetes. Diabetes 2008;57:1131–5.Google Scholar

  • 16.

    Borowiec M, Liew CW, Thompson R, Boonyasrisawat W, Hu J, et al. Mutations at the BLK locus linked to maturity onset diabetes of the young and beta-cell dysfunction. Proc Natl Acad Sci USA 2009;106:14460–5.CrossrefGoogle Scholar

  • 17.

    Bowman P, Flanagan SE, Edghill EL, Damhuis A, Shepherd MH, et al. Heterozygous ABCC8 mutations are a cause of MODY. Diabetologia 2012;55:123–7.CrossrefGoogle Scholar

  • 18.

    Bonnefond A, Philippe J, Durand E, Dechaume A, Huyvaert M, et al. Whole-exome sequencing and high throughput genotyping identified KCNJ11 as the thirteenth MODY gene. PLoS One 2012;7:e37423.CrossrefGoogle Scholar

  • 19.

    Johansson S, Irgens H, Chudasama KK, Molnes J, Aerts J, et al. Exome sequencing and genetic testing for MODY. PLoS One 2012;7:e38050.CrossrefGoogle Scholar

  • 20.

    Molven A, Njolstad PR. Role of molecular genetics in transforming diagnosis of diabetes mellitus. Expert Rev Mol Diagn 2011;11:313–20.Google Scholar

  • 21.

    Fajans SS, Bell GI, Polonsky KS. Molecular mechanisms and clinical pathophysiology of maturity-onset diabetes of the young. New Engl J Med 2001;345:971–80.CrossrefGoogle Scholar

  • 22.

    Naylor R, Philipson LH. Who should have genetic testing for maturity-onset diabetes of the young? Clin Endocrinol (Oxf) 2011;75:422–6.CrossrefGoogle Scholar

  • 23.

    Feigerlova E, Pruhova S, Dittertova L, Lebl J, Pinterova D, et al. Aetiological heterogeneity of asymptomatic hyperglycaemia in children and adolescents. Eur J Pediatr 2006;165:446–52.CrossrefGoogle Scholar

  • 24.

    Codner E, Rocha A, Deng L, Martinez-Aguayo A, Godoy C, et al. Mild fasting hyperglycemia in children: high rate of glucokinase mutations and some risk of developing Type 1 diabetes mellitus. Pediatr Diabetes 2009;10:382–8.Google Scholar

  • 25.

    Slingerland AS. Monogenic diabetes in children and young adults: challenges for researcher, clinician and patient. Rev Endocr Metab Disord 2006;7:171–85.Google Scholar

  • 26.

    McDonald TJ, Ellard S. Maturity onset diabetes of the young: identification and diagnosis. Ann Clin Biochem 2013;50 (Pt 5):403–15.CrossrefGoogle Scholar

  • 27.

    Cuesta-Munoz AL, Tuomi T, Cobo-Vuilleumier N, Koskela H, Odili S, et al. Clinical heterogeneity in monogenic diabetes caused by mutations in the glucokinase gene (GCK-MODY). Diabetes Care 2010;33:290–2.CrossrefGoogle Scholar

  • 28.

    Massa O, Meschi F, Cuesta-Munoz A, Caumo A, Cerutti F, et al. High prevalence of glucokinase mutations in Italian children with MODY. Influence on glucose tolerance, first-phase insulin response, insulin sensitivity and BMI. Diabetologia 2001;44:898–905.Google Scholar

  • 29.

    Velho G, Blanche H, Vaxillaire M, Bellanne-Chantelot C, Pardini VC, et al. Identification of 14 new glucokinase mutations and description of the clinical profile of 42 MODY-2 families. Diabetologia 1997;40:217–24.CrossrefGoogle Scholar

  • 30.

    Stride A, Shields B, Gill-Carey O, Chakera AJ, Colclough K, et al. Cross-sectional and longitudinal studies suggest pharmacological treatment used in patients with glucokinase mutations does not alter glycaemia. Diabetologia 2014;57:54–6.CrossrefGoogle Scholar

  • 31.

    Schober E, Rami B, Grabert M, Thon A, Kapellen T, et al. Phenotypical aspects of maturity-onset diabetes of the young (MODY diabetes) in comparison with Type 2 diabetes mellitus (T2DM) in children and adolescents: experience from a large multicentre database. Diabet Med 2009;26:466–73.CrossrefGoogle Scholar

  • 32.

    Martin D, Bellanne-Chantelot C, Deschamps I, Froguel P, Robert JJ, et al. Long-term follow-up of oral glucose tolerance test-derived glucose tolerance and insulin secretion and insulin sensitivity indexes in subjects with glucokinase mutations (MODY2). Diabetes Care 2008;31:1321–3.CrossrefGoogle Scholar

  • 33.

    Colom C, Corcoy R. Maturity onset diabetes of the young and pregnancy. Best Pract Res Clin Endocrinol Metab 2010;24:605–15.CrossrefGoogle Scholar

  • 34.

    Colclough K, Bellanne-Chantelot C, Saint-Martin C, Flanagan SE, Ellard S. Mutations in the genes encoding the transcription factors hepatocyte nuclear factor 1 alpha and 4 alpha in maturity-onset diabetes of the young and hyperinsulinemic hypoglycemia. Hum Mutat 2013;34:669–85.PubMedGoogle Scholar

  • 35.

    Cerf ME. Transcription factors regulating beta-cell function. Eur J Endocrinol 2006;155:671–9.CrossrefGoogle Scholar

  • 36.

    Galan M, Garcia-Herrero CM, Azriel S, Gargallo M, Duran M, et al. Differential effects of HNF-1alpha mutations associated with familial young-onset diabetes on target gene regulation. Mol Med 2011;17:256–65.Google Scholar

  • 37.

    Dukes ID, Sreenan S, Roe MW, Levisetti M, Zhou YP, et al. Defective pancreatic beta-cell glycolytic signaling in hepatocyte nuclear factor-1alpha-deficient mice. J Biol Chem 1998;273:24457–64.Google Scholar

  • 38.

    Hattersley AT. Maturity-onset diabetes of the young: clinical heterogeneity explained by genetic heterogeneity. Diabet Med 1998;15:15–24.Google Scholar

  • 39.

    Frayling TM, Bulamn MP, Ellard S, Appleton M, Dronsfield MJ, et al. Mutations in the hepatocyte nuclear factor-1alpha gene are a common cause of maturity-onset diabetes of the young in the U.K. Diabetes 1997;46:720–5.Google Scholar

  • 40.

    Bacon S, Kyithar MP, Schmid J, Rizvi SR, Bonner C, et al. Serum levels of pancreatic stone protein (PSP)/reg1A as an indicator of beta-cell apoptosis suggest an increased apoptosis rate in hepatocyte nuclear factor 1 alpha (HNF1A-MODY) carriers from the third decade of life onward. BMC Endocr Disord 2012;12:13.Google Scholar

  • 41.

    Harries LW, Ellard S, Stride A, Morgan NG, Hattersley AT. Isomers of the TCF1 gene encoding hepatocyte nuclear factor-1 alpha show differential expression in the pancreas and define the relationship between mutation position and clinical phenotype in monogenic diabetes. Hum Mol Genet 2006;15:2216–24.Google Scholar

  • 42.

    Hattersley A, Bruining J, Shield J, Njolstad P, Donaghue K, International Society for Pediatric and Adolescent Diabetes, et al. ISPAD Clinical Practice Consensus Guidelines 2006–2007. The diagnosis and management of monogenic diabetes in children. Pediatr Diabetes 2006;7:352–60.Google Scholar

  • 43.

    Stride A, Ellard S, Clark P, Shakespeare L, Salzmann M, et al. Beta-cell dysfunction, insulin sensitivity, and glycosuria precede diabetes in hepatocyte nuclear factor-1 alpha mutation carriers. Diabetes Care 2005;28:1751–6.Google Scholar

  • 44.

    Stride A, Vaxillaire M, Tuomi T, Barbetti F, Njolstad PR, et al. The genetic abnormality in the beta cell determines the response to an oral glucose load. Diabetologia 2002;45:427–35.CrossrefGoogle Scholar

  • 45.

    Pontoglio M, Prie D, Cheret C, Doyen A, Leroy C, et al. HNF1alpha controls renal glucose reabsorption in mouse and man. EMBO Rep 2000;1:359–65.Google Scholar

  • 46.

    Steele AM, Shields BM, Shepherd M, Ellard S, Hattersley AT, et al. Increased all-cause and cardiovascular mortality in monogenic diabetes as a result of mutations in the HNF1A gene. Diabet Med 2010;27:157–61.Google Scholar

  • 47.

    Stoffel M, Duncan SA. The maturity-onset diabetes of the young (MODY1) transcription factor HNF4alpha regulates expression of genes required for glucose transport and metabolism. Proc Natl Acad Sci USA 1997;94:13209–14.Google Scholar

  • 48.

    Pearson ER, Pruhova S, Tack CJ, Johansen A, Castleden HA, et al. Molecular genetics and phenotypic characteristics of MODY caused by hepatocyte nuclear factor 4alpha mutations in a large European collection. Diabetologia 2005;48:878–85.CrossrefGoogle Scholar

  • 49.

    Pearson ER, Boj SF, Steele AM, Barrett T, Stals K, et al. Macrosomia and hyperinsulinaemic hypoglycaemia in patients with heterozygous mutations in the HNF4A gene. PLoS Med 2007;4:e118.CrossrefGoogle Scholar

  • 50.

    Lehto M, Bitzen PO, Isomaa B, Wipemo C, Wessman Y, et al. Mutation in the HNF-4alpha gene affects insulin secretion and triglyceride metabolism. Diabetes 1999;48:423–5.Google Scholar

  • 51.

    Stoffers DA, Thomas MK, Habener JF. Homeodomain protein IDX-1: a master regulator of pancreas development and insulin gene expression. Trends Endocrin Met 1997;8:145–51.Google Scholar

  • 52.

    Schwitzgebel VM, Mamin A, Brun T, Ritz-Laser B, Zaiko M, et al. Agenesis of human pancreas due to decreased half-life of insulin promoter factor 1. J Clin Endocrinol Metab 2003;88:4398–406.Google Scholar

  • 53.

    Cockburn BN, Bermano G, Boodram LL, Teelucksingh S, Tsuchiya T, et al. Insulin promoter factor-1 mutations and diabetes in Trinidad: identification of a novel diabetes-associated mutation (E224K) in an Indo-Trinidadian family. J Clin Endocrinol Metab 2004;89:971–8.Google Scholar

  • 54.

    Gragnoli C, Stanojevic V, Gorini A, Von Preussenthal GM, Thomas MK, et al. IPF-1/MODY4 gene missense mutation in an Italian family with Type 2 and gestational diabetes. Metabolism 2005;54:983–8.Google Scholar

  • 55.

    Stoffers DA, Ferrer J, Clarke WL, Habener JF. Early-onset Type-II diabetes mellitus (MODY4) linked to IPF1. Nat Genet 1997;17:138–9.Google Scholar

  • 56.

    Fajans SS, Bell GI, Paz VP, Below JE, Cox NJ, et al. Obesity and hyperinsulinemia in a family with pancreatic agenesis and MODY caused by the IPF1 mutation Pro63fsX60. Transl Res 2010;156:7–14.Google Scholar

  • 57.

    Igarashi P, Shao X, McNally BT, Hiesberger T. Roles of HNF-1beta in kidney development and congenital cystic diseases. Kidney Int 2005;68:1944–7.Google Scholar

  • 58.

    Chen YZ, Gao Q, Zhao XZ, Chen YZ, Bennett CL, et al. Systematic review of TCF2 anomalies in renal cysts and diabetes syndrome/maturity onset diabetes of the young type 5. Chin Med J (Engl) 2010:123:3326–33.Google Scholar

  • 59.

    Edghill EL, Bingham C, Ellard S, Hattersley AT. Mutations in hepatocyte nuclear factor-1beta and their related phenotypes. J Med Genet 2006;43:84–90.Google Scholar

  • 60.

    Bellanne-Chantelot C, Chauveau D, Gautier JF, Dubois-Laforgue D, Clauin S, et al. Clinical spectrum associated with hepatocyte nuclear factor-1beta mutations. Ann Intern Med 2004;140:510–7.Google Scholar

  • 61.

    Bingham C, Bulman MP, Ellard S, Allen LI, Lipkin GW, et al. Mutations in the hepatocyte nuclear factor-1beta gene are associated with familial hypoplastic glomerulocystic kidney disease. Am J Hum Genet 2001;68:219–24.Google Scholar

  • 62.

    Ulinski T, Lescure S, Beaufils S, Guigonis V, Decramer S, et al. Renal phenotypes related to hepatocyte nuclear factor-1beta (TCF2) mutations in a pediatric cohort. J Am Soc Nephrol 2006;17:497–503.Google Scholar

  • 63.

    Edghill EL, Bingham C, Slingerland AS, Minton JA, Noordam C, et al. Hepatocyte nuclear factor-1 beta mutations cause neonatal diabetes and intrauterine growth retardation: support for a critical role of HNF-1beta in human pancreatic development. Diabet Med 2006;23:1301–6.Google Scholar

  • 64.

    Horikawa Y, Iwasaki N, Hara M, Furuta H, Hinokio Y, et al. Mutation in hepatocyte nuclear factor-1 beta gene (TCF2) associated with MODY. Nat Genet 1997;17:384–5.Google Scholar

  • 65.

    Pearson ER, Badman MK, Lockwood CR, Clark PM, Ellard S, et al. Contrasting diabetes phenotypes associated with hepatocyte nuclear factor-1alpha and -1beta mutations. Diabetes Care 2004;27:1102–7.Google Scholar

  • 66.

    Malecki MT, Jhala US, Antonellis A, Fields L, Doria A, et al. Mutations in NEUROD1 are associated with the development of Type 2 diabetes mellitus. Nat Genet 1999;23:323–8.Google Scholar

  • 67.

    Rubio-Cabezas O, Minton JA, Kantor I, Williams D, Ellard S, et al. Homozygous mutations in NEUROD1 are responsible for a novel syndrome of permanent neonatal diabetes and neurological abnormalities. Diabetes 2010;59:2326–31.Google Scholar

  • 68.

    Vaxillaire M, Bonnefond A, Froguel P. The lessons of early-onset monogenic diabetes for the understanding of diabetes pathogenesis. Best Pract Res Clin Endocrinol Metab 2012;26:171–87.CrossrefGoogle Scholar

  • 69.

    Kristinsson SY, Thorolfsdottir ET, Talseth B, Steingrimsson E, Thorsson AV, et al. MODY in Iceland is associated with mutations in HNF-1alpha and a novel mutation in NEUROD1. Diabetologia 2001;44:2098–103.Google Scholar

  • 70.

    Gonsorcikova L, Pruhova S, Cinek O, Ek J, Pelikanova T, et al. Autosomal inheritance of diabetes in two families characterized by obesity and a novel H241Q mutation in NEUROD1. Pediatr Diabetes 2008;9:367–72.Google Scholar

  • 71.

    Fernandez-Zapico ME, van Velkinburgh JC, Gutierrez-Aguilar R, Neve B, Froguel P, et al. MODY7 gene, KLF11, is a novel p300-dependent regulator of Pdx-1 (MODY4) transcription in pancreatic islet beta cells. J Biol Chem 2009;284:36482–90.Google Scholar

  • 72.

    Neve B, Fernandez-Zapico ME, Ashkenazi-Katalan V, Dina C, Hamid YH, et al. Role of transcription factor KLF11 and its diabetes-associated gene variants in pancreatic beta cell function. Proc Natl Acad Sci USA 2005;102:4807–12.CrossrefGoogle Scholar

  • 73.

    Johansson BB, Torsvik J, Bjorkhaug L, Vesterhus M, Ragvin A, et al. Diabetes and pancreatic exocrine dysfunction due to mutations in the carboxyl ester lipase gene-maturity onset diabetes of the young (CEL-MODY): a protein misfolding disease. J Biol Chem 2011;286:34593–605.CrossrefGoogle Scholar

  • 74.

    Raeder H, Johansson S, Holm PI, Haldorsen IS, Mas E, et al. Mutations in the CEL VNTR cause a syndrome of diabetes and pancreatic exocrine dysfunction. Nat Genet 2006;38:54–62.CrossrefGoogle Scholar

  • 75.

    Wang J, Elghazi L, Parker SE, Kizilocak H, Asano M, et al. The concerted activities of Pax4 and Nkx2.2 are essential to initiate pancreatic beta-cell differentiation. Dev Biol 2004;266:178–89.Google Scholar

  • 76.

    Habener JF, Kemp DM, Thomas MK. Minireview: transcriptional regulation in pancreatic development. Endocrinology 2005;146:1025–34.CrossrefGoogle Scholar

  • 77.

    Edghill EL, Flanagan SE, Patch AM, Boustred C, Parrish A, et al. Insulin mutation screening in 1,044 patients with diabetes: mutations in the INS gene are a common cause of neonatal diabetes but a rare cause of diabetes diagnosed in childhood or adulthood. Diabetes 2008;57:1034–42.CrossrefGoogle Scholar

  • 78.

    Raile K, O’Connell M, Galler A, Werther G, Kuhnen P, et al. Diabetes caused by insulin gene (INS) deletion: clinical characteristics of homozygous and heterozygous individuals. Eur J Endocrinol 2011;165:255–60.CrossrefGoogle Scholar

  • 79.

    Meur G, Simon A, Harun N, Virally M, Dechaume A, et al. Insulin gene mutations resulting in early-onset diabetes: marked differences in clinical presentation, metabolic status, and pathogenic effect through endoplasmic reticulum retention. Diabetes 2010;59:653–61.CrossrefGoogle Scholar

  • 80.

    Boesgaard TW, Pruhova S, Andersson EA, Cinek O, Obermannova B, et al. Further evidence that mutations in INS can be a rare cause of maturity-onset diabetes of the young (MODY). BMC Med Genet 2010;11:42.CrossrefGoogle Scholar

  • 81.

    Bonnefond A, Yengo L, Philippe J, Dechaume A, Ezzidi I, et al. Reassessment of the putative role of BLK-p.A71T loss-of-function mutation in MODY and Type 2 diabetes. Diabetologia 2013;56:492–6.CrossrefGoogle Scholar

  • 82.

    Pearson ER, Starkey BJ, Powell RJ, Gribble FM, Clark PM, et al. Genetic cause of hyperglycaemia and response to treatment in diabetes. Lancet 2003;362:1275–81.CrossrefGoogle Scholar

  • 83.

    Shepherd M, Shields B, Ellard S, Rubio-Cabezas O, Hattersley AT. A genetic diagnosis of HNF1A diabetes alters treatment and improves glycaemic control in the majority of insulin-treated patients. Diabet Med 2009;26:437–41.Google Scholar

  • 84.

    Lambert AP, Ellard S, Allen LI, Gallen IW, Gillespie KM, et al. Identifying hepatic nuclear factor 1alpha mutations in children and young adults with a clinical diagnosis of Type 1 diabetes. Diabetes Care 2003;26:333–7.Google Scholar

  • 85.

    Moller AM, Dalgaard LT, Pociot F, Nerup J, Hansen T, et al. Mutations in the hepatocyte nuclear factor-1alpha gene in Caucasian families originally classified as having Type I diabetes. Diabetologia 1998;41:1528–31.Google Scholar

  • 86.

    Kawasaki E, Sera Y, Yamakawa K, Abe T, Ozaki M, et al. Identification and functional analysis of mutations in the hepatocyte nuclear factor-1alpha gene in anti-islet autoantibody-negative Japanese patients with Type 1 diabetes. J Clin Endocrinol Metab 2000;85:331–5.Google Scholar

  • 87.

    Leslie RD, Atkinson MA, Notkins AL. Autoantigens IA-2 and GAD in Type I (insulin-dependent) diabetes. Diabetologia 1999;42:3–14.CrossrefGoogle Scholar

  • 88.

    Borg H, Marcus C, Sjoblad S, Fernlund P, Sundkvist G. Insulin autoantibodies are of less value compared with islet antibodies in the clinical diagnosis of autoimmune Type 1 diabetes in children older than 3 yr of age. Pediatr Diabetes 2002;3:149–54.Google Scholar

  • 89.

    Bowden SA, Hoffman RP. Triple diabetes: coexistence of Type 1 diabetes mellitus and a novel mutation in the gene responsible for MODY3 in an overweight adolescent. Pediatr Diabetes 2008;9:162–4.Google Scholar

  • 90.

    Calcaterra V, Martinetti M, Salina A, Aloi C, Larizza D. The coexistence of Type 1 diabetes, MODY2 and metabolic syndrome in a young girl. Acta Diabetol 2012;49:401–4.Google Scholar

  • 91.

    Urbanova J, Rypackova B, Kucera P, Andel M, Heneberg P. Should the negativity for islet cell autoantibodies be used in a prescreening for genetic testing in maturity-onset diabetes of the young? The case of autoimmunity-associated destruction of pancreatic beta-cells in a family of HNF1A-MODY subjects. Int Arch Allergy Immunol 2013;161:279–84.CrossrefGoogle Scholar

  • 92.

    Owen KR, Shepherd M, Stride A, Ellard S, Hattersley AT. Heterogeneity in young adult onset diabetes: aetiology alters clinical characteristics. Diabet Med 2002;19:758–61.CrossrefGoogle Scholar

  • 93.

    Gardner DS, Tai ES. Clinical features and treatment of maturity onset diabetes of the young (MODY). Diabetes Metab Syndr Obes 2012;5:101–8.CrossrefGoogle Scholar

  • 94.

    Shields BM, McDonald TJ, Ellard S, Campbell MJ, Hyde C, et al. The development and validation of a clinical prediction model to determine the probability of MODY in patients with young-onset diabetes. Diabetologia 2012;55:1265–72.CrossrefGoogle Scholar

  • 95.

    Stanik J, Dusatkova P, Cinek O, Valentinova L, Huckova M, et al. De novo mutations of GCK, HNF1A and HNF4A may be more frequent in MODY than previously assumed. Diabetologia 2014;57:480–4.CrossrefGoogle Scholar

  • 96.

    Owen KR, Thanabalasingham G, James TJ, Karpe F, Farmer AJ, et al. Assessment of high-sensitivity C-reactive protein levels as diagnostic discriminator of maturity-onset diabetes of the young due to HNF1A mutations. Diabetes Care 2010;33: 1919–24.Google Scholar

  • 97.

    Thanabalasingham G, Shah N, Vaxillaire M, Hansen T, Tuomi T, et al. A large multi-centre European study validates high-sensitivity C-reactive protein (hsCRP) as a clinical biomarker for the diagnosis of diabetes subtypes. Diabetologia 2011;54:2801–10.CrossrefGoogle Scholar

  • 98.

    McDonald TJ, Shields BM, Lawry J, Owen KR, Gloyn AL, et al. High-sensitivity CRP discriminates HNF1A-MODY from other subtypes of diabetes. Diabetes Care 2011;34:1860–2.CrossrefGoogle Scholar

  • 99.

    Besser RE, Shepherd MH, McDonald TJ, Shields BM, Knight BA, et al. Urinary C-peptide creatinine ratio is a practical outpatient tool for identifying hepatocyte nuclear factor 1-{alpha}/hepatocyte nuclear factor 4-{alpha} maturity-onset diabetes of the young from long-duration Type 1 diabetes. Diabetes Care 2011;34:286–91.Google Scholar

  • 100.

    Besser RE, Shields BM, Hammersley SE, Colclough K, McDonald TJ, et al. Home urine C-peptide creatinine ratio (UCPCR) testing can identify Type 2 and MODY in pediatric diabetes. Pediatr Diabetes 2013;14:181–8.Google Scholar

  • 101.

    Steele AM, Wensley KJ, Ellard S, Murphy R, Shepherd M, et al. Use of HbA1c in the identification of patients with hyperglycaemia caused by a glucokinase mutation: observational case control studies. PLoS One 2013;8:e65326.Google Scholar

  • 102.

    Hattersley A, Bruining J, Shield J, Njolstad P, Donaghue KC. The diagnosis and management of monogenic diabetes in children and adolescents. Pediatr Diabetes 2009;10(Suppl 12):33–42.CrossrefGoogle Scholar

  • 103.

    Chakera AJ, Carleton VL, Ellard S, Wong J, Yue DK, et al. Antenatal diagnosis of fetal genotype determines if maternal hyperglycemia due to a glucokinase mutation requires treatment. Diabetes Care 2012;35:1832–4.CrossrefGoogle Scholar

  • 104.

    Spyer G, Hattersley AT, Sykes JE, Sturley RH, MacLeod KM. Influence of maternal and fetal glucokinase mutations in gestational diabetes. Am J Obstet Gynecol 2001;185:240–1.CrossrefGoogle Scholar

  • 105.

    Fajans SS, Brown MB. Administration of sulfonylureas can increase glucose-induced insulin secretion for decades in patients with maturity-onset diabetes of the young. Diabetes Care 1993;16:1254–61.CrossrefGoogle Scholar

  • 106.

    Tuomi T, Honkanen EH, Isomaa B, Sarelin L, Groop LC. Improved prandial glucose control with lower risk of hypoglycemia with nateglinide than with glibenclamide in patients with maturity-onset diabetes of the young type 3. Diabetes Care 2006;29:189–94.CrossrefGoogle Scholar

  • 107.

    Docena MK, Faiman C, Stanley CM, Pantalone KM. Mody-3: novel HNF1A mutation and the utility of glucagon-like peptide (GLP)-1 receptor agonist therapy. Endocr Pract 2014;20:107–11.Google Scholar

  • 108.

    Becker M, Galler A, Raile K. Meglitinide analogues in adolescent patients with HNF1A-MODY (MODY 3). Pediatrics 2014;133:e775–9.CrossrefGoogle Scholar

About the article

Corresponding author: Ayhan Abacı, Department of Pediatric Endocrinology, Dokuz Eylul University, Balcova, Izmir, Turkey, Phone: +90-23-2412-6076, Fax: +90-23-2412-6005, E-mail:

Received: 2014-09-09

Accepted: 2014-11-24

Published Online: 2015-01-10

Published in Print: 2015-03-01

Citation Information: Journal of Pediatric Endocrinology and Metabolism, Volume 28, Issue 3-4, Pages 251–263, ISSN (Online) 2191-0251, ISSN (Print) 0334-018X, DOI: https://doi.org/10.1515/jpem-2014-0384.

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