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Maturity-onset diabetes of the young type 13(MODY13)

MedGen UID:
897640
Concept ID:
C4225365
Disease or Syndrome
Synonym: MODY, TYPE 13
 
Gene (location): KCNJ11 (11p15.1)
 
Monarch Initiative: MONDO:0014589
OMIM®: 616329

Definition

Maturity-onset diabetes of the young (MODY) is a group of several conditions characterized by abnormally high levels of blood glucose, also called blood sugar. These forms of diabetes typically begin before age 30, although they can occur later in life. In MODY, elevated blood glucose arises from reduced production of insulin, which is a hormone produced in the pancreas that helps regulate blood glucose levels. Specifically, insulin controls how much glucose (a type of sugar) is passed from the blood into cells, where it is used as an energy source.

The different types of MODY are distinguished by their genetic causes. The most common types are HNF1A-MODY (also known as MODY3), accounting for 50 to 70 percent of cases, and GCK-MODY (MODY2), accounting for 30 to 50 percent of cases. Less frequent types include HNF4A-MODY (MODY1) and renal cysts and diabetes (RCAD) syndrome (also known as HNF1B-MODY or MODY5), which each account for 5 to 10 percent of cases. At least ten other types have been identified, and these are very rare.

HNF1A-MODY and HNF4A-MODY have similar signs and symptoms that develop slowly over time. Early signs and symptoms in these types are caused by high blood glucose and may include frequent urination (polyuria), excessive thirst (polydipsia), fatigue, blurred vision, weight loss, and recurrent skin infections. Over time uncontrolled high blood glucose can damage small blood vessels in the eyes and kidneys. Damage to the light-sensitive tissue at the back of the eye (the retina) causes a condition known as diabetic retinopathy that can lead to vision loss and eventual blindness. Kidney damage (diabetic nephropathy) can lead to kidney failure and end-stage renal disease (ESRD). While these two types of MODY are very similar, certain features are particular to each type. For example, babies with HNF4A-MODY tend to weigh more than average or have abnormally low blood glucose at birth, even though other signs of the condition do not occur until childhood or young adulthood. People with HNF1A-MODY have a higher-than-average risk of developing noncancerous (benign) liver tumors known as hepatocellular adenomas.

GCK-MODY is a very mild type of the condition. People with this type have slightly elevated blood glucose levels, particularly in the morning before eating (fasting blood glucose). However, affected individuals often have no symptoms related to the disorder, and diabetes-related complications are extremely rare.

RCAD is associated with a combination of diabetes and kidney or urinary tract abnormalities (unrelated to the elevated blood glucose), most commonly fluid-filled sacs (cysts) in the kidneys. However, the signs and symptoms are variable, even within families, and not everyone with RCAD has both features. Affected individuals may have other features unrelated to diabetes, such as abnormalities of the pancreas or liver or a form of arthritis called gout. [from MedlinePlus Genetics]

Clinical features

From HPO
Diabetes mellitus
MedGen UID:
8350
Concept ID:
C0011849
Disease or Syndrome
A group of abnormalities characterized by hyperglycemia and glucose intolerance.
Hyperglycemia
MedGen UID:
5689
Concept ID:
C0020456
Disease or Syndrome
An increased concentration of glucose in the blood.
Gestational diabetes
MedGen UID:
38815
Concept ID:
C0085207
Disease or Syndrome
Gestational diabetes is a disorder characterized by abnormally high levels of blood glucose (also called blood sugar) during pregnancy. Affected women do not have diabetes before they are pregnant, and most of these women go back to being nondiabetic soon after the baby is born. The disease has a 30 to 70 percent chance of recurring in subsequent pregnancies. Additionally, about half of women with gestational diabetes develop another form of diabetes, known as type 2 diabetes, within a few years after their pregnancy.\n\nGestational diabetes is often discovered during the second trimester of pregnancy. Most affected women have no symptoms, and the disease is discovered through routine screening at their obstetrician's office. If untreated, gestational diabetes increases the risk of pregnancy-associated high blood pressure (called preeclampsia) and early (premature) delivery of the baby.\n\nBabies of mothers with gestational diabetes tend to be large (macrosomia), which can cause complications during birth. Infants whose mothers have gestational diabetes are also more likely to develop dangerously low blood glucose levels soon after birth. Later in life, these individuals have an increased risk of developing obesity, heart disease, and type 2 diabetes.
Maturity onset diabetes mellitus in young
MedGen UID:
87433
Concept ID:
C0342276
Disease or Syndrome
Maturity-onset diabetes of the young is an autosomal dominant form of diabetes typically occurring before 25 years of age and caused by primary insulin secretion defects. Despite its low prevalence, MODY is not a single entity but represents genetic, metabolic, and clinical heterogeneity (Vaxillaire and Froguel, 2008). Genetic Heterogeneity of MODY MODY1 (125850) is caused by heterozygous mutation in the hepatocyte nuclear factor-4-alpha gene (HNF4A; 600281) on chromosome 20. MODY2 (125851) is caused by heterozygous mutation in the glucokinase gene (GCK; 138079) on chromosome 7. MODY3 (600496) is caused by heterozygous mutation in the hepatocyte nuclear factor-1alpha gene (HNF1A; 142410) on chromosome 12q24. MODY4 (606392) is caused by heterozygous mutation in the pancreas/duodenum homeobox protein-1 gene (PDX1; 600733) on chromosome 13q12. MODY5 (137920) is caused by heterozygous mutation in the gene encoding hepatic transcription factor-2 (TCF2; 189907) on chromosome 17q12. MODY6 (606394) is caused by heterozygous mutation in the NEUROD1 gene (601724) on chromosome 2q31. MODY7 (610508) is caused by heterozygous mutation in the KLF11 gene (603301) on chromosome 2p25. MODY8 (609812), or diabetes-pancreatic exocrine dysfunction syndrome, is caused by heterozygous mutation in the CEL gene (114840) on chromosome 9q34. MODY9 (612225) is caused by heterozygous mutation in the PAX4 gene (167413) on chromosome 7q32. MODY10 (613370) is caused by heterozygous mutation in the insulin gene (INS; 176730) on chromosome 11p15. MODY11 (613375) is caused by heterozygous mutation in the BLK gene (191305) on chromosome 8p23. MODY13 (616329) is caused by heterozygous mutation in the KCNJ11 gene (600937) on chromosome 11p15. MODY14 (616511) is caused by heterozygous mutation in the APPL1 gene (604299) on chromosome 3p14.
Abnormality of body mass index
MedGen UID:
910555
Concept ID:
C3805014
Finding
Anomaly in the weight-to-height squared ratio, calculated by dividing the individual's weight in kilograms by the square of the individual's height in meters and used as an indicator of obesity and underweight compared to averages.
Elevated hemoglobin A1c
MedGen UID:
892798
Concept ID:
C4073162
Finding
An increased concentration of hemoglobin A1c (HbA1c), which is the product of nonenzymatic attachment of a hexose molecule to the N-terminal amino acid of the hemoglobin molecule. This reaction is dependent on blood glucose concentration, and therefore reflects the mean glucose concentration over the previous 8 to 12 weeks. The HbA1c level provides a better indication of long-term glycemic control than one-time blood or urinary glucose measurements.
Reduced C-peptide level
MedGen UID:
909412
Concept ID:
C4280764
Finding
A decreased concentration of C-peptide in the circulation. Since C-peptide is secreted in equimolar amounts to insulin, this feature correlates with reduced insulin secretion.
Anti-glutamic acid decarboxylase antibody positivity
MedGen UID:
1370651
Concept ID:
C4476703
Laboratory or Test Result
The presence of autoantibodies (immunoglobulins) in the serum that react against glutamic acid decarboxylase.

Professional guidelines

PubMed

Reilly F, Sanchez-Lechuga B, Clinton S, Crowe G, Burke M, Ng N, Colclough K, Byrne MM
Diabet Med 2020 May;37(5):876-884. Epub 2019 Oct 21 doi: 10.1111/dme.14145. PMID: 31562829
Leslie RD, Palmer J, Schloot NC, Lernmark A
Diabetologia 2016 Jan;59(1):13-20. doi: 10.1007/s00125-015-3789-z. PMID: 26498592
Faguer S, Decramer S, Chassaing N, Bellanné-Chantelot C, Calvas P, Beaufils S, Bessenay L, Lengelé JP, Dahan K, Ronco P, Devuyst O, Chauveau D
Kidney Int 2011 Oct;80(7):768-76. Epub 2011 Jul 20 doi: 10.1038/ki.2011.225. PMID: 21775974

Recent clinical studies

Etiology

Santos Monteiro S, da Silva Santos T, Fonseca L, Assunção G, Lopes AM, Duarte DB, Soares AR, Laranjeira F, Ribeiro I, Pinto E, Rocha S, Barbosa Gouveia S, Vazquez-Mosquera ME, Oliveira MJ, Borges T, Cardoso MH
Acta Diabetol 2023 Jan;60(1):83-91. Epub 2022 Oct 8 doi: 10.1007/s00592-022-01980-2. PMID: 36208343
Tosur M, Philipson LH
J Diabetes Investig 2022 Sep;13(9):1465-1471. Epub 2022 Jun 16 doi: 10.1111/jdi.13860. PMID: 35638342Free PMC Article
Li LM, Jiang BG, Sun LL
Front Endocrinol (Lausanne) 2022;13:829565. Epub 2022 Mar 1 doi: 10.3389/fendo.2022.829565. PMID: 35299962Free PMC Article
Menon S, Refaey A, Guffey D, Balasubramanyam A, Redondo MJ, Tosur M
Pediatr Diabetes 2022 Jun;23(4):447-456. Epub 2022 Mar 10 doi: 10.1111/pedi.13329. PMID: 35218126
Sagar RC, Phoenix F, Thanabalasingham G, Naseem K, Ajjan RA, Owen KR
Diab Vasc Dis Res 2020 Nov-Dec;17(6):1479164120963048. doi: 10.1177/1479164120963048. PMID: 33334146Free PMC Article

Diagnosis

Santos Monteiro S, da Silva Santos T, Fonseca L, Assunção G, Lopes AM, Duarte DB, Soares AR, Laranjeira F, Ribeiro I, Pinto E, Rocha S, Barbosa Gouveia S, Vazquez-Mosquera ME, Oliveira MJ, Borges T, Cardoso MH
Acta Diabetol 2023 Jan;60(1):83-91. Epub 2022 Oct 8 doi: 10.1007/s00592-022-01980-2. PMID: 36208343
Ge S, Yang M, Cui Y, Wu J, Xu L, Dong J, Liao L
Front Endocrinol (Lausanne) 2022;13:911526. Epub 2022 Jun 30 doi: 10.3389/fendo.2022.911526. PMID: 35846334Free PMC Article
Tosur M, Philipson LH
J Diabetes Investig 2022 Sep;13(9):1465-1471. Epub 2022 Jun 16 doi: 10.1111/jdi.13860. PMID: 35638342Free PMC Article
Sagar RC, Phoenix F, Thanabalasingham G, Naseem K, Ajjan RA, Owen KR
Diab Vasc Dis Res 2020 Nov-Dec;17(6):1479164120963048. doi: 10.1177/1479164120963048. PMID: 33334146Free PMC Article
Valkovicova T, Skopkova M, Stanik J, Gasperikova D
Endocr Regul 2019 Apr 1;53(2):110-134. doi: 10.2478/enr-2019-0013. PMID: 31517624

Therapy

Perge K, Nicolino M
Rev Endocr Metab Disord 2022 Oct;23(5):1063-1078. Epub 2022 Aug 23 doi: 10.1007/s11154-022-09749-2. PMID: 35996042
Pearson ER
Curr Opin Genet Dev 2018 Jun;50:68-73. Epub 2018 Feb 24 doi: 10.1016/j.gde.2018.02.005. PMID: 29486427
Heuvel-Borsboom H, de Valk HW, Losekoot M, Westerink J
Neth J Med 2016 Jun;74(5):193-200. PMID: 27323672
Pearson ER
Diabet Med 2016 Jun;33(6):712-7. doi: 10.1111/dme.13075. PMID: 26802434Free PMC Article
Fajans SS, Bell GI, Bowden DW, Halter JB, Polonsky KS
Diabet Med 1996 Sep;13(9 Suppl 6):S90-5. PMID: 8894490

Prognosis

Rottenkolber M, Gar C, Then C, Wanger L, Sacco V, Banning F, Potzel AL, Kern-Matschilles S, Nevinny-Stickel-Hinzpeter C, Grallert H, Hesse N, Seissler J, Lechner A
J Clin Endocrinol Metab 2021 Apr 23;106(5):1460-1471. doi: 10.1210/clinem/dgab057. PMID: 33515032Free PMC Article
Li M, Gong S, Han X, Zhang S, Ren Q, Cai X, Luo Y, Zhou L, Zhang R, Liu W, Zhu Y, Zhou X, Sun Y, Li Y, Ma Y, Ji L
J Diabetes 2021 Jul;13(7):542-553. Epub 2021 Jan 4 doi: 10.1111/1753-0407.13144. PMID: 33300273
Heuvel-Borsboom H, de Valk HW, Losekoot M, Westerink J
Neth J Med 2016 Jun;74(5):193-200. PMID: 27323672
Pearson ER
Diabet Med 2016 Jun;33(6):712-7. doi: 10.1111/dme.13075. PMID: 26802434Free PMC Article
Hattersley AT
J Pediatr Endocrinol Metab 2000;13 Suppl 6:1411-7. doi: 10.1515/jpem-2000-s615. PMID: 11202217

Clinical prediction guides

Menon S, Refaey A, Guffey D, Balasubramanyam A, Redondo MJ, Tosur M
Pediatr Diabetes 2022 Jun;23(4):447-456. Epub 2022 Mar 10 doi: 10.1111/pedi.13329. PMID: 35218126
Rottenkolber M, Gar C, Then C, Wanger L, Sacco V, Banning F, Potzel AL, Kern-Matschilles S, Nevinny-Stickel-Hinzpeter C, Grallert H, Hesse N, Seissler J, Lechner A
J Clin Endocrinol Metab 2021 Apr 23;106(5):1460-1471. doi: 10.1210/clinem/dgab057. PMID: 33515032Free PMC Article
Li M, Gong S, Han X, Zhang S, Ren Q, Cai X, Luo Y, Zhou L, Zhang R, Liu W, Zhu Y, Zhou X, Sun Y, Li Y, Ma Y, Ji L
J Diabetes 2021 Jul;13(7):542-553. Epub 2021 Jan 4 doi: 10.1111/1753-0407.13144. PMID: 33300273
Heuvel-Borsboom H, de Valk HW, Losekoot M, Westerink J
Neth J Med 2016 Jun;74(5):193-200. PMID: 27323672
Pearson ER
Diabet Med 2016 Jun;33(6):712-7. doi: 10.1111/dme.13075. PMID: 26802434Free PMC Article

Recent systematic reviews

Chen Y, Hu X, Zhao M
J Diabetes 2024 Mar;16(3):e13520. Epub 2023 Dec 14 doi: 10.1111/1753-0407.13520. PMID: 38095268Free PMC Article
Perge K, Nicolino M
Rev Endocr Metab Disord 2022 Oct;23(5):1063-1078. Epub 2022 Aug 23 doi: 10.1007/s11154-022-09749-2. PMID: 35996042
Ge S, Yang M, Cui Y, Wu J, Xu L, Dong J, Liao L
Front Endocrinol (Lausanne) 2022;13:911526. Epub 2022 Jun 30 doi: 10.3389/fendo.2022.911526. PMID: 35846334Free PMC Article

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