Diagnosis of MODY – brief overview for clinical practice

Česká verzia

Authors: Jana Urbanová ¹; Ludmila Brunerová ¹; Jan Brož ²
Authors place of work: Diabetologické centrum II. interní kliniky 3. LF UK a FN Královské Vinohrady, Praha ¹; Interní klinika 2. LF UK a FN Motol, Praha ²
Published in the journal: Vnitř Lék 2018; 64(4): 367-374
Category: Přehledné referáty

Summary

Maturity Onset Diabetes of the Young (MODY) comprises inherited forms of diabetes mellitus caused by the mutations in the genes involved in the development, differentiation and function of beta-cells. The majority of patients with MODY remains misdiagnosed and erroneously classified as type 1 or type 2 diabetic patients. Correct MODY diagnosis is, however, essential since it enables individualization of treatment, assessment of the prognosis and identification of diabetes among patient´s relatives. Clinical presentation of MODY is highly variable and it could resemble other types of diabetes, thus identification of MODY patients might be difficult. In this review, we describe typical clinical presentation of the most common MODY subtypes, we summarize current diagnostic guidelines in confirmation of MODY and we raise the question of possible need for extension of current clinical criteria indicating a patient for molecular-genetic testing.

Key words:
clinical course – diagnosis – differential diagnosis – glucokinase – hepatocyte nuclear factors – MODY

Zdroje

1. Tattersall RB. Mild familial diabetes with dominant inheritance. QJ Med 1974; 43(170): 339–357.

2. Průhová Š, Ek J, Lébl J et al. Genetic epidemiology of MODY in the Czech Republic: Novel mutations in the MODY genes HNF-4α, GCK and HNF-1α. Diabetologia 2003; 46(2): 291–295.

3. Shepherd M, Ellis I, Ahmad AM et al. Predictive genetic testing in maturity-onset diabetes of the young (MODY). Diabet Med 2001; 18(5): 417–421.

4. Shepherd M, Miles S, Jones J et al. Differential diagnosis: Identifying people with monogenic diabetes. J Diabetes Nurs 2010; 14(9): 342–347.

5. Byrne MM, Sturis J, Clement K et al. Insulin secretory abnormalities in subjects with hyperglycemia due to glucokinase mutations. J Clin Invest 1994; 93(3): 1120–1130. Dostupné z DOI: <http://dx.doi.org/10.1172/JCI117064>.

6. Ellard S, Bellanné-Chantelot C, Hattersley AT. [European Molecular Genetics Quality Network (EMQN) MODY group]. Best practice guidelines for the molecular genetic diagnosis of maturity-onset diabetes of the young. Diabetologia 2008; 51(4): 546–553. Dostupné z DOI: <http://dx.doi.org/10.1007/s00125–008–0942-y>.

7. Stride A, Vaxillaire M, Tuomi T et al. The genetic abnormality in the beta cell determines the response to an oral glucose load. Diabetologia 2002; 45(3): 427–435. Dostupné z DOI: <http://dx.doi.org/10.1007/s00125–001–0770–9>.

8. Steele AM, Wensley KJ, Ellard S 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(6): e65326. Dostupné z DOI: <http://dx.doi.org/10.1371/journal.pone.0065326>.

9. Stride A, Shields B, Gill-Carey O et al. Cross-sectional and longitudinal studies suggest pharmacological treatment used in patients with glucokinase mutations does not alter glycaemia. Diabetologia 2014; 57(1): 54–56. Dostupné z DOI: <http://dx.doi.org/10.1007/s00125–013–3075-x>.

10. Spyer G, Hattersley AT, Sykes JE et al. Influence of maternal and fetal glucokinase mutations in gestational diabetes. Am J Obstet Gynecol 2001; 185(1): 240–241. Dostupné z DOI: <http://dx.doi.org/10.1067/mob.2001.113127>.

11. Bacon S, Kyithar MP, Schmid J 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. Dostupné z DOI: <http://dx.doi.org/10.1186/1472–6823–12–13>.

12. Yamagata K. Roles of HNF1α and HNF4α in pancreatic β-cells: lessons from a monogenic form of diabetes (MODY). Vitam Horm 2014; 95: 407–423. Dostupné z DOI: <http://dx.doi.org/10.1016/B978–0-12–800174–5.00016–8>.

13. Stride A, Hattersley AT. Different genes, different diabetes: lessons from maturity-onset diabetes of the young. Ann Med 2002; 34(3): 207–216.

14. Pontoglio M, Prié D, Cheret C et al. HNF1alpha controls renal glucose reabsorption in mouse and man. EMBO Rep 2000; 1(4): 359–365. Dostupné z DOI: <http://dx.doi.org/10.1093/embo-reports/kvd071>.

15. Pearson ER, Pruhova S, Tack CJ 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): 878–885. Dostupné z DOI: <http://dx.doi.org/10.1007/s00125–005–1738-y>.

16. Murphy R. Monogenic diabetes and pregnancy. Obstet Med 2015; 8(3): 114–120. Dostupné z DOI: <http://dx.doi.org/10.1177/1753495X15590713>.

17. Stride A, Shepherd M, Frayling TM et al. Intrauterine hyperglycemia is associated with an earlier diagnosis of diabetes in HNF-1α gene mutation carriers. Diabetes Care 2002; 25(12): 2287–2291.

18. Stride A, Ellard S, Clark P et al. Beta-cell dysfunction, insulin sensitivity, and glycosuria precede diabetes in hepatocyte nuclear factor-1alpha mutation carriers. Diabetes Care 2005; 28(7): 1751–1756.

19. McDonald TJ, McEneny J, Pearson ER et al. Lipoprotein composition in HNF1A-MODY: Differentiating between HNF1A-MODY and Type 2 diabetes. Clin Chim Acta 2012; 413(9-10): 927–932.

20. Thanabalasingham G, Pal A, Selwood MP 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(6): 1206–1212. Dostupné z DOI: <http://dx.doi.org/10.2337/dc11–1243>.

21. Isomaa B, Henricsson M, Lehto M et al. Chronic diabetic complications in patients with MODY3 diabetes. Diabetologia 1998; 41(4): 467–473. Dostupné z DOI: <http://dx.doi.org/10.1007/s001250050931>.

22. Steele AM, Shields BM, Shepherd M et al. Increased all-cause and cardiovascular mortality in monogenic diabetes as a result of mutations in the HNF1A gene. Diabet Med 2010; 27(2): 157–161. Dostupné z DOI: <http://dx.doi.org/10.1111/j.1464–5491.2009.02913.x>.

23. Coffinier C, Thepot D, Babinet C et al. Essential role for the homeoprotein vHNF1/HNF1beta in visceral endoderm differentiation. Development 1999; 126(21): 4785–4794.

24. Ulinski T, Lescure S, Beaufils S et al. Renal phenotypes related to hepatocyte nuclear factor-1beta (TCF2) mutations in a pediatric cohort. J Am Soc Nephrol 2006; 17(2): 497–503. Dostupné z DOI: <http://dx.doi.org/10.1681/ASN.2005101040>.

25. Edghill EL, Bingham C, Ellard S et al. Mutations in hepatocyte nuclear factor-1beta and their related phenotypes. J Med Genet 2005; 43(1): 84–90. Dostupné z DOI: <http://dx.doi.org/10.1136/jmg.2005.032854>.

26. Pearson ER, Badman MK, Lockwood CR et al. Contrasting diabetes phenotypes associated with hepatocyte nuclear factor-1alpha and -1beta mutations. Diabetes Care 2004; 27(5): 1102–1107.

27. Edghill EL, Bingham C, Slingerland AS 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(12): 1301–1306. Dostupné z DOI: <http://dx.doi.org/10.1111/j.1464–5491.2006.01999.x>.

28. Gardner DS, Tai ES. Clinical features and treatment of maturity onset diabetes of the young (MODY). Diabetes Metab Syndr Obes 2012; 5: 101–108. Dostupné z DOI: <http://dx.doi.org/10.2147/DMSO.S23353>.

29. MODY Probability Calculator. Dostupné z WWW: <http://www.diabetesgenes.org/content/mody-probability-calculator>.

30. Shields BM, McDonald TJ, Ellard S 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(5): 1265–1272. Dostupné z DOI: <http://dx.doi.org/10.1007/s00125–011–2418–8>.

31. Hattersley AT, Beards F, Ballantyne E et al. Mutations in the glucokinase gene of the fetus result in reduced birth weight. Nat Genet 1998; 19(3): 268–270. Dostupné z DOI: <http://dx.doi.org/10.1038/953>.

32. Ellard S, Beards F, Allen LIS et al. A high prevalence of glucokinase mutations in gestational diabetic subjects selected by clinical criteria. Diabetologia 2000; 43(2): 250–253. Dostupné z DOI: <http://dx.doi.org/10.1007/s001250050038>.

33. Chakera AJ, Spyer G, Vincent N et al. The 0.1% of the Population With Glucokinase Monogenic Diabetes Can Be Recognized by Clinical Characteristics in Pregnancy: The Atlantic Diabetes in Pregnancy Cohort. Diabetes Care May 2014; 37(5): 1230–1236. Dostupné z DOI: <http://dx.doi.org/10.2337/dc13–2248>.

34. Murphy R, Ellard S, Hattersley AT. Clinical implications of a molecular genetic classification of monogenic β-cell diabetes. Nat Clin Pract Endocrinol Metab 2008; 4(4): 200–213. Dostupné z DOI: <http://dx.doi.org/10.1038/ncpendmet0778>.

35. Owen KR, Shepherd M, Stride A et al. Heterogeneity in young adult onset aetiology alters clinical characteristics. Diabet Med 2002; 19(9): 758–761.

36. McDonald TJ, Shields BM, Lawry J et al. High-sensitivity CRP discriminates HNF1A-MODY from other subtypes of diabetes. Diabetes Care 2011; 34: 1860–1862. Dostupné z DOI: <http://dx.doi.org/10.2337/dc11–0323>.

37. Besser REJ, Shepherd MJ, McDonald TJ et al. Urinary C-peptide creatinine ratio (UCPCR) is a practical outpatient tool for identifying HNF1A/HNF4A MODY from long duration Type 1 diabetes. Diabetes Care 2011; 34(2): 286–291. Dostupné z DOI: <http://dx.doi.org/10.2337/dc10–1293>.

38. Sagen JV, Pearson ER, Johansen A et al. Preserved insulin response to tolbutamide in HNF-1alpha mutation carriers. Diabet Med 2005; 22(4): 406–409. Dostupné z DOI: <http://dx.doi.org/10.1111/j.1464–5491.2005.01439.x>.

39. Pearson ER, Boj SF, Steele AM et al. Macrosomia and hyperinsulinaemic hypoglycaemia in patients with heterozygous mutations in the HNF4A gene. PLoS Med 2007; 4(4): e118. Dostupné z DOI: <http://dx.doi.org/10.1371/journal.pmed.0040118>.

40. Grzanka M, Matejko B, Szopa M et al. Assessment of Newly Proposed Clinical Criteria to Identify HNF1A MODY in Patients with an Initial Diagnosis of Type 1 or Type 2 Diabetes Mellitus. Adv Med 2016; 2016: 4243784. Dostupné z DOI: <http://dx.doi.org/10.1155/2016/4243784>.

41. Petruzelkova L, Dusatkova P, Cinek O et al. Substantial proportion of MODY among multiplex families participating in a Type 1 diabetes prediction programme. Diabet Med 2016; 33(12): 1712–1716. Dostupné z DOI: <http://dx.doi.org/10.1111/dme.13043>.

42. Bellanne-Chantelot C, Chauveau D, Gautier JF et al. Clinical spectrum associated with hepatocyte nuclear factor-1beta mutations. Ann Intern Med 2004; 140(7): 510–517.

43. Chen YZ, Gao Q, Zhao XZ 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(22): 3326–3333.

44. Adalat S, Woolf AS, Johnstone KA et al. HNF1B mutations associate with hypomagnesemia and renal magnesium wasting. J Am Soc Nephrol 2009; 20(5): 1123–1131. Dostupné z DOI: <http://dx.doi.org/10.1681/ASN.2008060633>.

45. Bellanné-Chantelot C, Carette C, Riveline JP et al. The type and the position of HNF1A mutation modulate age at diagnosis of diabetes in patients with maturity-onset diabetes of the young (MODY)-3. Diabetes 2008; 57(2): 503–508. Dostupné z DOI: <http://dx.doi.org/10.2337/db07–0859>.

46. Lango Allen H, Johansson S, Ellard S et al. Polygenic risk variants for type 2 diabetes susceptibility modify age at diagnosis in monogenic HNF1A diabetes. Diabetes 2010; 59(1): 266–271. Dostupné z DOI: <http://dx.doi.org/10.2337/db09–0555>.

47. Klupa T, Warram JH, Antonellis A et al. Determinants of the development of diabetes (maturity-onset diabetes of the young-3) in carriers of HNF-1α mutations: evidence for parent-of-origin effect. Diabetes Care 2002; 25(12): 2292–2301.

48. Frayling TM, Evans JC, Bulman MP et al. Beta-cell genes and diabetes: molecular and clinical characterization of mutations in transcription factors. Diabetes 2001; 50(Suppl 1): S94-S100.

49. Shepherd M, Hattersley AT, Sparkes A. Genetic testing in maturity onset diabetes of the young (MODY): a new challenge for the diabetic clinic. Pract Diabetes 2001; 18(1): 16–21. Dostupné z DOI: <https://doi.org/10.1002/pdi.108>.

50. Knebel B, Mack S, Haas J et al. Divergent phenotypes in siblings with identical novel mutations in the HNF-1α gene leading to maturity onset diabetes of the young type 3. BMC Med Genet 2016; 17(1): 36. Dostupné z DOI: <http://dx.doi.org/10.1186/s12881–016–0297-z>.

51. Urbanová J, Hoffmanová I, Anděl M. Manifestace diabetes mellitus 1. typu u 97leté pacientky. DMEV 2011; 14(1): 22–24. Dostupné z WWW: <http://www.tigis.cz/images/stories/DMEV/2011/01/04_urbanova_dmev_1–11.pdf>.

52. McDonald TJ, Colclough K, Brown R et al. Islet autoantibodies can discriminate maturity-onset diabetes of the young (MODY) from Type 1 diabetes. Diabet Med 2011; 28(9): 1028–1033. Dostupné z DOI: <http://dx.doi.org/10.1111/j.1464–5491.2011.03287.x>.

53. Schober E, Rami B, Grabert M 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 multicenter database. Diabet Med 2009; 26(5): 466–473. Dostupné z DOI: <http://dx.doi.org/10.1111/j.1464–5491.2009.02720.x>.

54. Urbanová J, Rypáčková B, Procházková Z et al. Positivity for islet cell autoantibodies in patients with monogenic diabetes is associated with later diabetes onset and higher HbA1c level. Diabet Med 2014; 31(4): 466–471. Dostupné z DOI: <http://dx.doi.org/10.1111/dme.12314>.

55. Průhová Š, Dušátková P, Neumann D et al. Two cases of diabetic ketoacidosis in HNF1A-MODY linked to severe dehydration: is it time to change the diagnostic criteria for MODY? Diabetes Care 2013; 36(9): 2573–2574. Dostupné z DOI: <http://dx.doi.org/10.2337/dc13–0058>.

56. Stanik J, Dusatkova P, Cinek O et al. De novo mutations of GCK, HNF1A and HNF4A may be more frequent in MODY than previously assumed. Diabetologia 2014; 57(3): 480–484. Dostupné z DOI: <http://dx.doi.org/10.1007/s00125–013–3119–2>.

57. Shields BM, Hicks S, Shepherd MH et al. Maturity-onset diabetes of the young (MODY): how many cases are we missing? Diabetologia 2010; 53(12): 2504–2508. Dostupné z DOI: <http://dx.doi.org/10.1007/s00125–010–1799–4>.

58. Shields BM, Shepherd M, Hudson M et al. Population-Based Assessment of a Biomarker-Based Screening Pathway to Aid Diagnosis of Monogenic Diabetes in Young-Onset Patients. Diabetes Care 2017; 40(8): 1017–1025. Dostupné z DOI: <http://dx.doi.org/10.2337/dc17–0224>.

59. Hattersley AT, Patel KA. Precision diabetes: learning from monogenic diabetes. Diabetologia 2017; 60(5): 769–777. Dostupné z DOI: <http://dx.doi.org/10.1007/s00125–017–4226–2>.

60. Anık A, Çatlı G, Abacı A et al. Maturity-onset diabetes of the young (MODY): an update. J Pediatr Endocrinol Metab 2015; 28(3–4): 251–263. Dostupné z DOI: <http://dx.doi.org/10.1515/jpem-2014–0384>.

61. Škrha J, Pelikánová T, Kvapil M. Doporučený postup péče o diabetes mellitus 2. typu. Česká diabetologická společnost ČLS JEP 2017. Dostupné z WWW: <http://www.diab.cz/dokumenty/standard_lecba_dm_typ_II.pdf>.