Maturity-onset diabetes of the young (MODY): Recognition is the need of the hour.
Keywords:
Maturity Onset Diabetes of Young (MODY), gene mutation, monogenic diabetes
Abstract
Maturity-onset diabetes of the young (MODY) is a monogenic form of diabetes that is characterized by autosomal dominant mode of inheritance, an early onset diabetes, mostly mild hyperglycemia as a result of a primary defect in pancreatic β-cell function. MODY represents less than 2% of all diabetes cases and is commonly misdiagnosed as type 1 or type 2 diabetes mellitus. It is a genetically heterogeneous form of monogenic diabetes that is caused by mutations occurring in a number of different genes thus tends to cause a slightly different variant of diabetes. At least 14 MODY subtypes with distinct genetic etiologies have been identified to date. MODY is typically diagnosed during late childhood, adolescence, or early adulthood and is usually observed to develop in adults during their late 50's. One of the main drawbacks in its diagnosis is that many people with MODY are misdiagnosed as having type 1 or type 2 diabetes owing to low index of suspicion and lack of availability of genetic testing at affordable cost. However, a molecular and genetic diagnosis results in a better treatment and could also help in identifying other family members with MODY. A high index of suspicion is required to diagnose cases of MODY as misdiagnosis and inappropriate treatment may have a significant impact on quality of life (QOL) with increased cost and unnecessary treatment with insulin.
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References
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5. 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.
6. Fajans SS, Bell GI. MODY: history, genetics, pathophysiology, and clinical decision making. Diabetes Care 2011;34:1878–84.
7. 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.
8. Fajans SS, Conn JW. Prediabetes, subclinical diabetes and latent clinical diabetes: interpretation, diagnosis and treatment. Nat Treat Diabetes 1965;641–656.
9. Tattersall RB. Mild familial diabetes with dominant inheritance. Q J Med 1974 ;43:339–57.
10. 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.
11. Johansen K, Gregersen G. A family with dominantly inherited mild juvenile diabetes. Acta Med Scand 1977;201:567–70.
12. 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.
13. Nelson PG, Pyke DA. Genetic diabetes not linked to the HLA locus. Br Med J 1976;24;1:196–7.
14. Johnston C, Owerbach D, Leslie RDG, Pyke DA, Nerup J. Mason-type diabetes and DNA insertion polymorphism. The Lancet 1984;323:280.
15. Galler A, Stange T, Müller G, Näke A, Vogel C, Kapellen T, et al. Incidence of childhood diabetes in children aged less than 15 years and its clinical and metabolic characteristics at the time of diagnosis: data from the Childhood Diabetes Registry of Saxony, Germany. Horm Res Paediatr 2010;74:285–91.
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17. Schober E, Rami B, Grabert M, Thon A, Kapellen T, Reinehr 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 J Br Diabet Assoc 2009;26:466–73.
18. 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.
19. 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.
20. Pihoker C, Gilliam LK, Ellard S, Dabelea D, Davis C, Dolan LM, 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.
21. Ledermann HM. Is maturity onset diabetes at young age (MODY) more common in Europe than previously assumed? Lancet Lond Engl 1995;345(8950):648.
22. Panzram G, Adolph W. Heterogeneity of maturity onset diabetes at young age (MODY). Lancet Lond Engl 1981;2:986.
23. Mohan V, Ramachandran A, Snehalatha C, Mohan R, Bharani G, Viswanathan M. High prevalence of maturity-onset diabetes of the young (MODY) among Indians. Diabetes Care 1985;8:371–4.
24. Johansen K. Mild diabetes in young subjects. Clinical aspects and plasma insulin response pattern. Acta Med Scand 1973;193:23–33.
25. Barbosa J, Ramsay R, Goetz FC. Plasma glucose, insulin, glucagon, and growth hormone in kindreds with maturity-onset type of hyperglycemia in young people. Ann Intern Med 1978;88:595–601.
26. Faber OK, Thomsen M, Binder C, Platz P, Svejgaard A. HLA antigens in a family with maturity-onset type diabetes mellitus. Acta Endocrinol (Copenh) 1978;88:329–38.
27. Serjeantson S, Zimmet P. Diabetes in the Pacific: evidence for a major gene. Diabetes Mellit Recent Knowl Aetiol Complicat Treat 1984;23–30.
28. Asmal AC, Dayal B, Jialal I, Leary WP, Omar MA, Pillay NL, et al. Non-insulin-dependent diabetes mellitus with early onset in Blacks and Indians. South African Medical Journal Suid-Afrikaanse Tydskrif Vir Geneeskunde. 1981;60:93–6.
29. Johansson S, Irgens H, Chudasama KK, Molnes J, Aerts J, et al. Exome sequencing and genetic testing for MODY. PLoS One 2012;7:e38050.
30. Molven A, Njolstad PR. Role of molecular genetics in transforming diagnosis of diabetes mellitus. Expert Rev Mol Diagn 2011;11:313–20.
31. Froguel P, Vaxillaire M, Sun F, Velho G, Zouali H, Butel MO, Lesage S, Vionnet N, Clement K, Fougerousse F, et al. Close Linkage Of Glucokinase Locus On Chromosome 7p To Early-Onset Non-Insulin-Dependent Diabetes Mellitus. Nature 1992;356:162–164.
32. Hattersley AT, Turner RC, Permutt MA, Patel P, Tanizawa Y, Chiu KC, O’Rahilly S, Watkins PJ, Wainscoat JS: Linkage Of Type 2 Diabetes To The Glucokinase Gene. Lancet 1992:339:1307–1310.
33. Yamagata K, Furuta H, Oda N, Kalsaki PJ, Menzel S, Cox NJ, Fajans SS, Signorini S, Stoffel M, Bell G. Mutations In The Hepatocyte Nuclear Factor-4-Alpha Gene In Maturity-Onset Diabetes Of The Young (MODY1). Nature 1996;384:458-460.
34. Yamagata K, et al. Mutations In The Hepatocyte Nuclear Factor-1 alpha Gene In Maturity-Onset Diabetes Of The Young (MODY3). Nature 1996;384:455–458.
35 Harries LW, Ellard S, Stride A, Morgan NG, Hattersley AT. Isomers of the TCF1 gene encoding hepatocyte nuclear factor-1alpha 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.
36 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.
37 Stoffrs DA, Ferrer J, Clarke WL, Habener JF. Early-onset type II diabetes mellitus (MODY4) linked to IPF1. Nat Genet 1997;17:138-9.
38 Schwitzgebel VM, Mamin A, Brun T, Ritz-Laser B, Zaiko M, Maret A, Jornayvaz FR, Theintz GE, Michielin O, Melloul D, Philippe J. Agenesis of human pancreas due to decreased half life of insulin promoter factor 1. J Clin Endocrinol Metab 2003;88:4398-406.
39 Horikawa Y, Iwasaki N, Hara M, Furuta H, Hinokio Y, Cockburn BN, Lindner T, Yamagata K, Ogata M, Tomonaga O, Kuroki H, Kasahara T, Iwamoto Y, Bell GI. Mutation in hepatocyte nuclear factor-1 beta gene (TCF2) associated with MODY. Nat Genet 1997;17:384-5.
40 Edghill EL, Bingham C, Slingerland AS, Minton JA, Noordam C, Ellard S, Hattersley AT. 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.
41 Bellanne-Chantelot C, Chauveau D, Gautier JF, Dubois-Laforgue D, Clauin S, Beaufis S, Wilhelm JM, Boitard C, Noel LH, Velho G, Timsit J. Clinical spectrum associated with hepatocyte nuclear factor-1beta mutations. Ann Intern Med 2004;140:510-7.
42 Malecki MT, Jhala US, Antonellis A, Fields L, Doria A, Orban T, Saad M, Warram JH, Montminy M, Krolewski AS. Mutations in NEUROD1 are associated with the development of type 2 diabetes mellitus. Nat Genet 1999;23:323-8.
43 Gonsorcikova L, Pruhova S, Cinek O, Ek J, Pelikanova T, Jorgensen T, Eiberg H, Pedersen O, Hansen T, Lebl J. Autosomal inheritance of diabetes in two families characterized by obesity and a novel H241Q mutation in NEUROD1. Pediatr Diabetes 2008;9:367-72.
44 Rubio-Cabezas O, Minton JA, Kantor I, Williams D, Ellard S, Hattersley AT. Homozygous mutations in NEUROD1 are responsible for a novel syndrome of permanent neonatal diabetes and neurological abnormalities. Diabetes 2010;59:2326-31.
45 Johansson BB, Torsvik J, Bjorkhaug L, Vesterhus M, Ragvin A, Tjora E, Fjeld K, Hoem D, Johansson S, Raeder H, Lindquist S, Hernell O, Cnop M, Saraste J, Flatmark T, Molven A, Njolstad PR. 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
46 Bowman P, Flanagan SE, Edghill EL, Damhuis A, Shepherd MH, Paisey R, Hattersley AT, Ellard S. Heterozygous ABCC8 mutations are a cause of MODY. Diabetologia 2012;55:123-7.
47 Bonnefond A, Philippe J, Durand E, Dechaume A, Huyvaert M, Montagne L, Marre M, Balkau B, Fajardy I, Vambergue A, Vatin V, Delplanque J, Le Guilcher D, De Graeve F, Lecoeur C, Sand O, Vaxillaire M, Froguel P. Whole-exome sequencing and high throughput genotyping identified KCNJ11 as the thirteenth MODY gene. PLoS One 2012;7:e37423.
48 Shepherd M, Sparkes AC, Hattersley AT. Genetic testing in maturity onset diabetes of the young (MODY): a new challenge for the diabetic clinic. Pract Diabetes Int 2001;18:16–21.
49 Rubio-Cabezas O, Hattersley AT, Njolstad PR, Clinical Practice Consensus Guidelines ISPAD, et al. The diagnosis and management of monogenic diabetes in children and adolescents. Pediatr Diabetes 2014;15:47–64.
50 Kavvoura FK, Owen KR. Maturity onset diabetes of the young: clinical characteristics, diagnosis and management. Pediatr Endocrinol Rev 2012;10:234-42.
51 Ellard S, Lango Allen H, De Franco E, Flanagan SE, Hysenaj G, Colclough K, Houghton JA, Shepherd M, Hattersley AT, Weedon MN, Caswell R. Improved genetic testing for monogenic diabetes using targeted next-generation sequencing. Diabetologia 2013;56:1958-63.
52 Thanabalasingham G, Pal A, Selwood MP, Dudley C, Fisher K, Bingley PJ, Ellard S, Farmer AJ, McCarthy MI, Owen KR. 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.
53 Shields BM, McDonald TJ, Ellard S, Campbell MJ, Hyde C, Hattersley AT. Th 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.
54 McDonald TJ, Shields BM, Lawry J, Owen KR, Gloyn AL, Ellard S, et al. High-sensitivity CRP discriminates HNF1A-MODY from other subtypes of diabetes. Diabetes Care 2011;34:1860–2.
55 Owen KR, Thanabalasingham G, James TJ, Karpe F, Farmer AJ, McCarthy MI, 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.
56 Thanabalasingham G, Huffman JE, Kattla JJ, et al. Mutations in HNF1A result in marked alterations of plasma glycan profile. Diabetes 2013;62:1329–37.
57 Bacon S, Kyithar MP, Schmid J, et al. Circulating CD36 is reduced in HNF1A-MODY carriers. PLoS One. 2013 Sep 12.8(9):e74577.
58 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.
59 Hattersley A, Bruining J, Shield J, Njolstad P, DonaghueKC. The diagnosis and management of monogenic diabetes in children and adolescents. Pediatr Diabetes 2009;10:33–42.
60 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.
61 Pearson ER, Pruhova S, Tack CJ, Johansen A, Castleden HA, et al. Molecular genetics and phenotypic characteristics of MODY caused by hepatocyte nuclear factor 4-alpha mutations in a large European collection. Diabetologia 2005;48:878–85.
62 Laver TW, Colclough K, Shepherd M, Patel K, Houghton JA, Dusatkova P, Pruhova S, Morris AD, Palmer CN, McCarthy MI, Ellard S, Hattersley AT, Weedon MN. The common p.R114W HNF4A mutation causes a distinct clinical subtype of monogenic diabetes. Diabetes 2016; 65:3212-7.
63 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.
64 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.
65 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.
2. Available from: http://www.diabetesatlas.org/across-the-globe.html.
3. Ogurtsova K, Fernandes JD da R, Huang Y, Linnenkamp U, Guariguata L, Cho NH, et al. IDF Diabetes Atlas: Global estimates for the prevalence of diabetes for 2015 and 2040. Diabetes Res Clin Pract 2017;128:40–50.
4. 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.
5. 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.
6. Fajans SS, Bell GI. MODY: history, genetics, pathophysiology, and clinical decision making. Diabetes Care 2011;34:1878–84.
7. 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.
8. Fajans SS, Conn JW. Prediabetes, subclinical diabetes and latent clinical diabetes: interpretation, diagnosis and treatment. Nat Treat Diabetes 1965;641–656.
9. Tattersall RB. Mild familial diabetes with dominant inheritance. Q J Med 1974 ;43:339–57.
10. 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.
11. Johansen K, Gregersen G. A family with dominantly inherited mild juvenile diabetes. Acta Med Scand 1977;201:567–70.
12. 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.
13. Nelson PG, Pyke DA. Genetic diabetes not linked to the HLA locus. Br Med J 1976;24;1:196–7.
14. Johnston C, Owerbach D, Leslie RDG, Pyke DA, Nerup J. Mason-type diabetes and DNA insertion polymorphism. The Lancet 1984;323:280.
15. Galler A, Stange T, Müller G, Näke A, Vogel C, Kapellen T, et al. Incidence of childhood diabetes in children aged less than 15 years and its clinical and metabolic characteristics at the time of diagnosis: data from the Childhood Diabetes Registry of Saxony, Germany. Horm Res Paediatr 2010;74:285–91.
16. Neu A, Feldhahn L, Ehehalt S, Hub R, Ranke MB, DIARY group Baden-Württemberg. Type 2 diabetes mellitus in children and adolescents is still a rare disease in Germany: a population-based assessment of the prevalence of type 2 diabetes and MODY in patients aged 0-20 years. Pediatr Diabetes 2009;10:468–73.
17. Schober E, Rami B, Grabert M, Thon A, Kapellen T, Reinehr 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 J Br Diabet Assoc 2009;26:466–73.
18. 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.
19. 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.
20. Pihoker C, Gilliam LK, Ellard S, Dabelea D, Davis C, Dolan LM, 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.
21. Ledermann HM. Is maturity onset diabetes at young age (MODY) more common in Europe than previously assumed? Lancet Lond Engl 1995;345(8950):648.
22. Panzram G, Adolph W. Heterogeneity of maturity onset diabetes at young age (MODY). Lancet Lond Engl 1981;2:986.
23. Mohan V, Ramachandran A, Snehalatha C, Mohan R, Bharani G, Viswanathan M. High prevalence of maturity-onset diabetes of the young (MODY) among Indians. Diabetes Care 1985;8:371–4.
24. Johansen K. Mild diabetes in young subjects. Clinical aspects and plasma insulin response pattern. Acta Med Scand 1973;193:23–33.
25. Barbosa J, Ramsay R, Goetz FC. Plasma glucose, insulin, glucagon, and growth hormone in kindreds with maturity-onset type of hyperglycemia in young people. Ann Intern Med 1978;88:595–601.
26. Faber OK, Thomsen M, Binder C, Platz P, Svejgaard A. HLA antigens in a family with maturity-onset type diabetes mellitus. Acta Endocrinol (Copenh) 1978;88:329–38.
27. Serjeantson S, Zimmet P. Diabetes in the Pacific: evidence for a major gene. Diabetes Mellit Recent Knowl Aetiol Complicat Treat 1984;23–30.
28. Asmal AC, Dayal B, Jialal I, Leary WP, Omar MA, Pillay NL, et al. Non-insulin-dependent diabetes mellitus with early onset in Blacks and Indians. South African Medical Journal Suid-Afrikaanse Tydskrif Vir Geneeskunde. 1981;60:93–6.
29. Johansson S, Irgens H, Chudasama KK, Molnes J, Aerts J, et al. Exome sequencing and genetic testing for MODY. PLoS One 2012;7:e38050.
30. Molven A, Njolstad PR. Role of molecular genetics in transforming diagnosis of diabetes mellitus. Expert Rev Mol Diagn 2011;11:313–20.
31. Froguel P, Vaxillaire M, Sun F, Velho G, Zouali H, Butel MO, Lesage S, Vionnet N, Clement K, Fougerousse F, et al. Close Linkage Of Glucokinase Locus On Chromosome 7p To Early-Onset Non-Insulin-Dependent Diabetes Mellitus. Nature 1992;356:162–164.
32. Hattersley AT, Turner RC, Permutt MA, Patel P, Tanizawa Y, Chiu KC, O’Rahilly S, Watkins PJ, Wainscoat JS: Linkage Of Type 2 Diabetes To The Glucokinase Gene. Lancet 1992:339:1307–1310.
33. Yamagata K, Furuta H, Oda N, Kalsaki PJ, Menzel S, Cox NJ, Fajans SS, Signorini S, Stoffel M, Bell G. Mutations In The Hepatocyte Nuclear Factor-4-Alpha Gene In Maturity-Onset Diabetes Of The Young (MODY1). Nature 1996;384:458-460.
34. Yamagata K, et al. Mutations In The Hepatocyte Nuclear Factor-1 alpha Gene In Maturity-Onset Diabetes Of The Young (MODY3). Nature 1996;384:455–458.
35 Harries LW, Ellard S, Stride A, Morgan NG, Hattersley AT. Isomers of the TCF1 gene encoding hepatocyte nuclear factor-1alpha 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.
36 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.
37 Stoffrs DA, Ferrer J, Clarke WL, Habener JF. Early-onset type II diabetes mellitus (MODY4) linked to IPF1. Nat Genet 1997;17:138-9.
38 Schwitzgebel VM, Mamin A, Brun T, Ritz-Laser B, Zaiko M, Maret A, Jornayvaz FR, Theintz GE, Michielin O, Melloul D, Philippe J. Agenesis of human pancreas due to decreased half life of insulin promoter factor 1. J Clin Endocrinol Metab 2003;88:4398-406.
39 Horikawa Y, Iwasaki N, Hara M, Furuta H, Hinokio Y, Cockburn BN, Lindner T, Yamagata K, Ogata M, Tomonaga O, Kuroki H, Kasahara T, Iwamoto Y, Bell GI. Mutation in hepatocyte nuclear factor-1 beta gene (TCF2) associated with MODY. Nat Genet 1997;17:384-5.
40 Edghill EL, Bingham C, Slingerland AS, Minton JA, Noordam C, Ellard S, Hattersley AT. 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.
41 Bellanne-Chantelot C, Chauveau D, Gautier JF, Dubois-Laforgue D, Clauin S, Beaufis S, Wilhelm JM, Boitard C, Noel LH, Velho G, Timsit J. Clinical spectrum associated with hepatocyte nuclear factor-1beta mutations. Ann Intern Med 2004;140:510-7.
42 Malecki MT, Jhala US, Antonellis A, Fields L, Doria A, Orban T, Saad M, Warram JH, Montminy M, Krolewski AS. Mutations in NEUROD1 are associated with the development of type 2 diabetes mellitus. Nat Genet 1999;23:323-8.
43 Gonsorcikova L, Pruhova S, Cinek O, Ek J, Pelikanova T, Jorgensen T, Eiberg H, Pedersen O, Hansen T, Lebl J. Autosomal inheritance of diabetes in two families characterized by obesity and a novel H241Q mutation in NEUROD1. Pediatr Diabetes 2008;9:367-72.
44 Rubio-Cabezas O, Minton JA, Kantor I, Williams D, Ellard S, Hattersley AT. Homozygous mutations in NEUROD1 are responsible for a novel syndrome of permanent neonatal diabetes and neurological abnormalities. Diabetes 2010;59:2326-31.
45 Johansson BB, Torsvik J, Bjorkhaug L, Vesterhus M, Ragvin A, Tjora E, Fjeld K, Hoem D, Johansson S, Raeder H, Lindquist S, Hernell O, Cnop M, Saraste J, Flatmark T, Molven A, Njolstad PR. 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
46 Bowman P, Flanagan SE, Edghill EL, Damhuis A, Shepherd MH, Paisey R, Hattersley AT, Ellard S. Heterozygous ABCC8 mutations are a cause of MODY. Diabetologia 2012;55:123-7.
47 Bonnefond A, Philippe J, Durand E, Dechaume A, Huyvaert M, Montagne L, Marre M, Balkau B, Fajardy I, Vambergue A, Vatin V, Delplanque J, Le Guilcher D, De Graeve F, Lecoeur C, Sand O, Vaxillaire M, Froguel P. Whole-exome sequencing and high throughput genotyping identified KCNJ11 as the thirteenth MODY gene. PLoS One 2012;7:e37423.
48 Shepherd M, Sparkes AC, Hattersley AT. Genetic testing in maturity onset diabetes of the young (MODY): a new challenge for the diabetic clinic. Pract Diabetes Int 2001;18:16–21.
49 Rubio-Cabezas O, Hattersley AT, Njolstad PR, Clinical Practice Consensus Guidelines ISPAD, et al. The diagnosis and management of monogenic diabetes in children and adolescents. Pediatr Diabetes 2014;15:47–64.
50 Kavvoura FK, Owen KR. Maturity onset diabetes of the young: clinical characteristics, diagnosis and management. Pediatr Endocrinol Rev 2012;10:234-42.
51 Ellard S, Lango Allen H, De Franco E, Flanagan SE, Hysenaj G, Colclough K, Houghton JA, Shepherd M, Hattersley AT, Weedon MN, Caswell R. Improved genetic testing for monogenic diabetes using targeted next-generation sequencing. Diabetologia 2013;56:1958-63.
52 Thanabalasingham G, Pal A, Selwood MP, Dudley C, Fisher K, Bingley PJ, Ellard S, Farmer AJ, McCarthy MI, Owen KR. 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.
53 Shields BM, McDonald TJ, Ellard S, Campbell MJ, Hyde C, Hattersley AT. Th 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.
54 McDonald TJ, Shields BM, Lawry J, Owen KR, Gloyn AL, Ellard S, et al. High-sensitivity CRP discriminates HNF1A-MODY from other subtypes of diabetes. Diabetes Care 2011;34:1860–2.
55 Owen KR, Thanabalasingham G, James TJ, Karpe F, Farmer AJ, McCarthy MI, 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.
56 Thanabalasingham G, Huffman JE, Kattla JJ, et al. Mutations in HNF1A result in marked alterations of plasma glycan profile. Diabetes 2013;62:1329–37.
57 Bacon S, Kyithar MP, Schmid J, et al. Circulating CD36 is reduced in HNF1A-MODY carriers. PLoS One. 2013 Sep 12.8(9):e74577.
58 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.
59 Hattersley A, Bruining J, Shield J, Njolstad P, DonaghueKC. The diagnosis and management of monogenic diabetes in children and adolescents. Pediatr Diabetes 2009;10:33–42.
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Published
2019-12-04
How to Cite
1.
Bhat JA, Bhat MH, Masoodi SR. Maturity-onset diabetes of the young (MODY): Recognition is the need of the hour. jms [Internet]. 2019Dec.4 [cited 2026Oct.2];22(2):3-11. Available from: http://ano.jmsskims.org/index.php/jms/article/view/486
Section
Review Articles
This work is licensed under a Creative Commons Attribution 4.0 International License.
