Monogenic diabetes – an unappreciated problem among physicians

Authors

  • Elżbieta Niechciał Department of Pediatric Diabetes and Obesity, Poznan University of Medical Sciences, Poland
  • Bogda Skowrońska Department of Pediatric Diabetes and Obesity, Poznan University of Medical Sciences, Poland
  • Anna Gertig-Kolasa Department of Pediatric Diabetes and Obesity, Poznan University of Medical Sciences, Poland
  • Izabela Krzyśko Department of Pediatric Diabetes and Obesity, Poznan University of Medical Sciences, Poland
  • Piotr Fichna Department of Pediatric Diabetes and Obesity, Poznan University of Medical Sciences, Poland

DOI:

https://doi.org/10.20883/medical.e57

Keywords:

monogenic diabetes, prevalence, diagnosis, treatment

Abstract

Monogenic diabetes results from one or more mutations in a single gene. It is a relatively rare genetic condition, therefore, it was frequently unappreciated among clinicians. Consequently, monogenic diabetes is misdiagnosed as type 1 diabetes or type 2 diabetes. Such misclassification leads to an inappropriate treatment, often inconvenient for the patients, such as insulin injections with their permanent glycemic control. The correct diagnosis may completely change previous methods of treatment. Patients diagnosed with GCK mutations may be completely treated with adequate diet. HNF1A/HNF4A affected patients are extremely sensitive to low dose sulphonylureas. Moreover, the exact diagnosis has an impact on patients’ relatives. Mostly, misdiagnosing of monogenic diabetes is caused by its rare occurrence and insufficient training in this area among physicians. According to different studies it may comprise 1–4% of all cases of diabetes. The aim of this article is to emphasize that despite the fact that monogenic diabetes is an uncommon disease, it should always be considered in cases of diabetes with unusual course.

Downloads

Download data is not yet available.

References

Matschinsky F, Liang Y, Kesavan P, et al. Glucokinase as pancreatic beta cell glucose sensor and diabetes gene. J Clin Invest. 1993;92:2092.

Gloyn AL, Pearson ER, Antcliff JF, Proks P, Bruining GJ, Slingerland AS, et al. Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes. N Engl J Med. 2004;350(18):1838–49.

Hansen T, Eiberg H, Rouard M, et al. Novel MODY3 mutations in the hepatocyte nuclear factor-1alpha gene: evidence for a hyperexcitability of pancreatic beta-cells to intravenous secretagogues in a glucose-tolerant carrier of a P447L mutation. Diabetes. 1997;46:726.

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(2):171–87, DOI: 10.1016/j.beem.2011.12.001.

Hattersley AT. Molecular genetics goes to the diabetes clinic. Clin Med. 2005;5(5):476–81.

Molven A, Njolstad PR. Role of molecular genetics in transforming diagnosis of diabetes mellitus. Expert Rev Mol Diagn. 2011;11(3):313–20, DOI: 10.1586/erm.10.123.

Temple IK, Gardner RJ, Mackay DJ, Barber JC, Robinson DO, Shield JP. Transient neonatal diabetes: widening the understanding of the etiopathogenesis of diabetes. Diabetes. 2000;49(8):1359–66.

Slingerland, AS, Shields BM, Flanagan SE, Bruining GJ, Noordam K, Gach A, et al. Referral rates for diagnostic testing support an incidence of permanent neonatal diabetes in three European countries of at least 1 in 260,000 live births. Diabetologia. 2009;52:1683–5.

Babenko AP, Polak M, Cave H, Busiah K, Czernichow P, Scharfmann R. Activating mutations in the ABCC8 gene in neonatal diabetes mellitus. N Engl J Med. 2006;355: 456–66.

Flanagan SE, Patch AM, Mackay DJ, Edghill EL, Gloyn AL, Robinson D, et al. Mutations in ATP-sensitive K+ channel genes cause transient neonatal diabetes and permanent diabetes in childhood or adulthood. Diabetes. 2007;56: 1930–7.

Pearson ER, Flechtner I, Njolstad PR, Malecki MT, Flanagan SE, Larkin B, et al. Neonatal Diabetes International Collaborative Group. Switching from insulin to oral sulfonylureas in patients with diabetes due to Kir6.2 mutations. N Engl J Med. 2006;355(5):467–77.

Fajans S, Bell G, Polonsky K. Molecular Mechanisms and Clinical Pathophysiology of Maturity-Onset Diabetes of the Young. N Engl J Med. 2001;345:971–980, DOI: 10.1056/NEJMra002168.

Shields BM, Hicks S, Shepherd MH, Colclough K, Hattersley AT, Ellard S. Maturity-onset diabetes of the young (MODY): how many cases are we missing? Diabetologia. 2010;53(12):2504–8, DOI: 10.1007/s00125–010–1799–4.

Schober E, Rami B, Grabert M, Thon A, Kapellen T, Reinehr T. 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(5):466–73, DOI: 10.1111/j.1464–5491.2009.02720.x.

Moller AM, Dalgaard LT, Pociot F, Nerup J, Hansen T, Pedersen O. Mutations in the hepatocyte nuclear factor-1alpha gene in Caucasian families originally classified as having Type I diabetes. Diabetologia. 1998;41(12):1528–31.

Slingerland AS, Hattersley AT. Mutations in the Kir6.2 subunit of the KATP channel and permanent neonatal diabetes: new insights and new treatment. Ann Med. 2005;37(3):186–95.

Ellard S, Allen LI, Gallen IW, Gillespie KM, Bingley PJ, Hattersley AT. Identifying hepatic nuclear factor 1alpha mutations in children and young adults with a clinical diagnosis of type 1 diabetes. Lambert AP. Diabetes Care. 2003;26(2):333–7.

Murphy R, Ellard S, Hattersley AT. Clinical implications of a molecular genetic classification of monogenic bold beta-cell diabetes. Nat Clin Pract Endocrinol Metab. 2008;4:200–13, DOI: 10.1038/ ncpendmet0778.

Cano A, Molines L, Valéro R, Simonin G, Paquis-Flucklinger V, Vialettes B. Microvascular Diabetes Complications in Wolfram Syndrome (Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy, and Deafness [DIDMOAD]): An age- and duration-matched comparison with common type 1 diabetes. Diabetes Care. 2007;30:2327–30; published ahead of print May 29, 2007, DOI: 10.2337/dc07–0380.

Marshall JD, Maffei P, Collin GB, Naggert JK. Alström syndrome: genetics and clinical overview. 20. Curr Genomics. 2011;12(3):225–35, DOI: 10.2174/138920211795677912.

http://www.medscape.com/viewarticle/807533.

Shankar RK, Pihoker C, Dolan LM, et al. Permanent neonatal diabetes mellitus: prevalence and genetic diagnosis in the SEARCH for Diabetes in Youth Study. Pediatr Diabetes. 2013;14(3):174–80, DOI: 10.1111/pedi.12003. Epub 2012 Oct 10.

Wiedemann B, Schober E, Waldhoer T, et al. Incidence of neonatal diabetes in Austria—calculation based on the Austrian Diabetes Register. Pediatr Diabetes. 2010;11: 18–23.

Eide SA, Raeder H, Johansson S, et al. Prevalence of HNF1A (MODY3) mutations in a Norwegian population (the HUNT2 Study). Diabet Med J Br Diabet Assoc. 2008;25:775–81.

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

Fendler W, Borowiec M, Baranowska-Jazwiecka A, et al. Prevalence of monogenic diabetes amongst Polish children after a nationwide genetic screening campaign. Diabetologia. 2012;55:2631–5.

American Diabetes Assosiation. Diagnosis and Classification of Diabetes Mellitus. Diabetes Care January. 2012; 35 (Suppl. 1):64–71.

Bingley PJ, Bonifacio E, Williams AJ, Genovese S, Bottazzo GF, Gale EA. Prediction of IDDM in the general population: strategies based on combinations of autoantibody markers. Diabetes. 1997;46(11):1701–10.

Sabbah E, Savola K, Ebeling T, Kulmala P, Vähäsalo P, Ilonen J, et al. Genetic, autoimmune, and clinical characteristics of childhood- and adult-onset type 1 diabetes. Diabetes Care. 2000;23(9):1326–32.

Wenzlau JM, Juhl K, Yu L, Moua O, Sarkar SA, Gottlieb P, et al. The cation efflux transporter ZnT8 (Slc30A8) is a major autoantigen in human type 1 diabetes. Proc Natl Acad Sci USA. 2007;104(43):17040–5. Epub 2007 Oct 17.

Borg H, Marcus C, Sjöblad S, Fernlund P, Sundkvist G. Islet cell antibody frequency differs from that of glutamic acid decarboxylase antibodies/IA2 antibodies after diagnosis of diabetes. Acta Paediatr. 2000;89(1):46–51.

McDonald TJ, Colclough K, Brown R, Shields B, Shepherd M, Bingley P, et al. Islet autoantibodies can discriminate maturity-onset diabetes of the young (MODY) from Type 1 diabetes. Diabet Med. 2011;28(9):1028–33, DOI: 10.1111/j.1464–5491.2011.03287.x.

Gilliam LK, Pihoker C, Ellard S, Hattersley AT, Dabelea D, Davis C, et al. for the SEARCH for Diabetes in Youth Study Group. 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 Jun 14.

Irgens HU, Molnes J, Johansson BB, Ringdal M, Skrivarhaug T, Undlien DE, et al. Prevalence of monogenic diabetes in the population-based Norwegian Childhood Diabetes Registry. Diabetologia. 2013;56(7):1512–9, DOI: 10.1007/s00125–013–2916-y. Epub 2013 Apr 27.

http://www.ispad.org/content/ispad-clinical-practice-consensus-guidelines-2009.

Thanabalasingham G, Owen KR. Clinical Review: Diagnosis and management of maturity onset diabetes of the young (MODY). BMJ. 2011;343, DOI: http://dx.doi.org/ 10.1136/bmj.d6044.

Hattersley AT, Pearson ER. Minireview: pharmacogenetics and beyond: the interaction of therapeutic response, beta-cell physiology, and genetics in diabetes. Endocrinology. 2006;147(6):2657–63. Epub 2006 Mar 23.

Stride A, Vaxillaire M, Tuomi T, Barbetti F, Njolstad PR, Hansen T, et al. The genetic abnormality in the beta cell determines the response to an oral glucose load. Diabetologia. 2002;45(3):427–35.

Velho G, Blanché H, Vaxillaire M, Bellanné-Chantelot C, Pardini VC, Timsit J, et al. Identification of 14 new glucokinase mutations and description of the clinical profile of 42 MODY-2 families. Diabetologia. 1997;40(2):217–24.

Pearson ER, Liddell WG, Shepherd M, et al. Sensitivity to sulphonylureas in patients with hepatocyte nuclear factor 1 alpha gene mutations: evidence for pharmacogenetics in diabetes. Diab Med. 2000;17:543–5.

Pearson ER, Starkey BJ, Powell RJ, et al. Genetic aetiology of hyperglycaemia determines response to treatment in diabetes. Lancet. 2003;362(9392):1275–81.

Delépine M, Nicolino M, Barrett T, Golamaully M, Lathrop GM, Julier C. EIF2AK3, encoding translation initiation factor 2-alpha kinase 3, is mutated in patients with Wolcott--Rallison syndrome. Nat Genet. 2000;25(4):406–9.

Byrne MM, Sturis J, Menzel S, Yamagata K, Fajans SS, Dronsfield MJ, et al. Altered insulin secretory responses to glucose in diabetic and nondiabetic subjects with mutations in the diabetes susceptibility gene MODY3 on chromosome 12. Diabetes. 1996;45(11):1503–10.

Pearson ER, Pruhova S, Tack CJ, Johansen A, Castleden HA, Lumb PJ, et al. Molecular genetics and phenotypic characteristics of MODY caused by hepatocyte nuclear factor 4alpha mutations in a large European collection. Diabetologia. 2005;48(5):878–85. Epub 2005 Apr 14.

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(9):1254–61.

Downloads

Published

2014-06-30

How to Cite

1.
Niechciał E, Skowrońska B, Gertig-Kolasa A, Krzyśko I, Fichna P. Monogenic diabetes – an unappreciated problem among physicians. JMS [Internet]. 2014 Jun. 30 [cited 2024 Mar. 29];83(2):132-7. Available from: https://jms.ump.edu.pl/index.php/JMS/article/view/57

Issue

Section

Review Papers
Received 2016-02-17
Published 2014-06-30