Conclusions the molecular and clinical features of gck. This profile detects pathogenic variants and copy number variants in the coding sequence and exonintron junctions of the four genes most commonly involved in mody. Clinical features and treatment of maturity onset diabetes of. Mody 2 is due to any of several mutations in the gck gene on chromosome 7 for glucokinase. Normal glucokinase triggers insulin secretion as the glucose exceeds about 90 mgdl 5 mm. Inactivating heterozygous mutations in the glucokinase gene gck cause a form of monogenic diabetes with autosomal dominant inheritance gck matureonset diabetes of the young mody 1,2. Genetic testing of gckmody identifies a novel pathogenic. Glucokinase serves as the glucose sensor for the pancreatic beta cell. Gck analysis for maturity onset diabetes of the young type 2. The second most common cause is gck mody due to heterozygous mutations in the. Clinical features and treatment of maturity onset diabetes. Diagnosis and management of glucokinase monogenic diabetes. When to consider a diagnosis of mody at the presentation.
There is scarcity of information on the clinical features and genetics of glucokinasematurityonset diabetes of the young gck mody in china. Mody is inherited in an autosomal dominant pattern and estimated to account for 12% of all diabetes. Hyperglycemia, diabetes, gck mody, latinamerica background maturityonset diabetes of the young mody is a rare monogenic disease which accounts for 12% of all diabetes cases 1, 2. Oct 19, 2011 maturity onset diabetes of the young mody comprises a heterogeneous group of monogenic disorders characterised by.
Mody is caused by a mutation or change in a single gene. Changes in the gck gene can lead to increases in blood glucose and affected people may be diagnosed with diabetes although this rise in blood glucose is mild and usually does not need treatment. Correctly identifying gck mody is important because these women have a different clinical course both within and outside pregnancy compared to standard gestational diabetes. Their molecular diagnosis is expensive but promotes the improvement of genetic counseling and treatment 3. Gckmody mody 2 monogenic diabetes at university of.
Maturityonset diabetes of the young mody or monogenic diabetes is an autosomal dominant form of noninsulindependent diabetes that typically presents before the age of 25 years 1. Out of fourteen, up to date discovered, mody genes omim, 2016 the most often affected ones include gck gene encoding glucokinase enzyme and. Apr 28, 2020 maturityonset diabetes of the young 2 mody2. Maturity onset diabetes of the young mody is a heterogeneous group of disorders that result in. Diagnosis and management of glucokinase monogenic diabetes in.
The mpc was higher than 75% in 11 subjects including all five cases with hnf1a mutations. Mody is a rare condition, accounting for 15% of all cases of diabetes 12, and 16% of pediatric cases of diabetes. Glucokinasematurityonset diabetes of the young gck mody is an autosomal dominant disorder caused by heterozygous inactivating gck gene mutations. Gckmody has generally been considered a phenotypically homogenous mild form of diabetes, which does not lead to marked hyperglycemia or diabetes complications and does not need. The most frequent subtypes are due to mutations of the gck mody 2, hnf1a mody 3, and hnf4a mody 1 genes. Genetic and clinical characteristics of chinese children. Monogenic diabetes mody three gene evaluation gck,hnf1a, hnf1b monogenic diabetes mody four gene evaluation gck,hnf1a, hnf1b, hnf4a informed consent required. What does it mean if there is a change in the gck gene. Pregnancy outcome of japanese patients with glucokinase. Mody maturity onset diabetes of the young is a specific type of diabetes caused by mutation in a single gene, involved in the development and function of the. We undertook the first multicenter genetic study of mody in the portuguese population. These mody genes encode the enzymes glucokinase gck mody 2 that is liable for the early processing of glucose in the.
Hyperglycemia, diabetes, gckmody, latinamerica background maturityonset diabetes of the young mody is a rare monogenic disease which accounts for 12% of all diabetes cases 1, 2. Gck mody is one the most common mody subtypes, affecting 0. We therefore determined the relative contributions of hyperglycemia and iatrogenic hyperinsulinemia to insulin resistance using hyperinsulinemiceuglycemic clamps in three participant groups n 10group with differing insulinemia and glycemia. Gck mody is greater than in the control subjects, thereby potentially reducing insulin sensitivity in the subjects with gck mody. Mody should be suspected in nonobese subjects, onset before 25 years with mild hyperglycemia and absence of. Discuss the major characteristics of mody and list the 3 most common types.
Mody probability calculator for gck and hnf1a screening in a. May 01, 2012 maturity onset diabetes of the young mody is a heterogeneous group of disorders that result in. What does maturityonset diabetes of the young mody look like determining which type of diabetes a patient has is critical in providing the proper care and treatment. Mody and 40 additional family members with hyperglycaemia whose genetic status was unknown, only one had diabetic nephropathy. We have previously demonstrated the potential economic bene. Management in patients with diabetes due a mutations of. Maturityonset diabetes of the young mody is a frequently misdiagnosed type of diabetes, which is characterized by early onset, autosomal dominant inheritance, and absence of insulin dependence. Strategies to select the ideal subjects to screen for monogenic dm mdm in different. Full text maturityonset diabetes of the young mody.
For adults who do not need immediate insulin treatment, a default diagnosis of type 2 diabetes is the most common outcome, but a small proportion of patients will actually have maturityonset diabetes of the young mody. Gck mody is characterized by stable, mild hyperglycemia without typical longterm diabetes complications. Since all pregnant women undergo glycemic assessment, there is an opportunity to identify women with gck mody within the. Hyperglycemia is present at birth but often only detected later in life, when individuals undergo routine screening tests 1. Genes involved in mody 4 molecular genetic studies demonstrated that mody is a clinically and hereditarily heterogeneous responsible for mody table. Timely diagnosis and appropriate treatment of diabetes is a keystone of patient man. Description mody is a form of niddm 125853 characterized by monogenic autosomal dominant transmission and early age of onset.
Welsh, rn, msn, cpnp nemours aiduponthospital for children objectives. Maturityonset diabetes of the young mody is a rare monogenic disease which accounts for 12% of all diabetes cases 1, 2. A form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood usually before 25 years of age, a primary defect in insulin secretion and frequent insulinindependence at the beginning of the disease. Gckmody in the us national monogenic diabetes registry. Results hnf1amody and gckmody groups had similar mean age 41. If a parent has this gene mutation, any child they have, has a 50% chance of inheriting it from them. Maturityonset diabetes of the young mody in portugal. Mody is a genetic heterogeneous condition for which today seven causal genes have been identified. Letter to editor maturity onset diabetes of the young mody. A survey was distributed via redcap to 94 women 18 years enrolled in the university of chicago monogenic diabetes registry. It is estimated to be the underlying cause of diabetes in 12% of patients diagnosed with diabetes, but prevalence estimates will not be accurate until large population screening studies are performed. The aim of the study was to investigate the clinical and molecular characteristics of chinese children with gck mody. Quality of life assessment in patients with hnf1amody and. Diagnosis and management of maturity onset diabetes of the.
Mody is most commonly caused by mutations in genes encoding the transcription factors hnf1a, hnf4a, and hnf1b, and the glycolytic enzyme glucokinase gck. Since then, gck mutations have been described throughout the world and are routinely tested for in many countries. In the hnf1a group, five of 27 individuals had mutations 18. Clinical heterogeneity in monogenic diabetes caused by. Heterozygous mutations in the glucokinase gck gene were first recognized as a cause of maturityonset diabetes of the young mody in 1992 1,2, and this led to the recognition that gckmody is a discrete type of diabetes hyperglycemia 2,3. Identifying patients with gdm at risk for gckmody diabetes. Affected individuals maintain their fasting glucose levels at a higher set point 5.
Jan 14, 2020 prevalence of maturityonset diabetes of the young mody is estimated between 1 and 2% of all diabetes cases. Mody has been believed to be rare in asian people, and only a few case reports have been published. We also recruited participants with type 1 diabetes with glycemia matching that of the group with gck mody. Demystifying maturityonset diabetes of the young mody. It is rare, accounting for just 1%2% of all diabetes. Recently 14 genes associated with mody have been proposed and the clinical characteristics differ according to the genetic etiology 3. Mody 2 is a form of maturity onset diabetes of the young. The aim of this study was to examine clinical management and pregnancy outcomes amongst women with a known diagnosis of gckmody. Approximately one third of the studied patients have gck or hnf1a. Molecular reductions in glucokinase activity increase. In 16 french families with maturityonset diabetes of the young mody2. Gdm mothers are at very high risk of developing type 2 diabetes in the 10 years following diagnosis while gck patients are likely to have stable glucose intolerance deteriorating only slightly with time 1 in gdm, offspring will almost certainly have normal glucose tolerance. Eleven children with asymptomatic hyperglycemia and clinically. Glucokinase serves as a glucose sensor in pancreatic cells.
Mody is a rare form of diabetes which is different from both type 1 and type 2 diabetes, and runs strongly in families. It is often misdiagnosed as type 1 or type 2 diabetes, as it is often difficult to distinguish mody from these two forms. However, a rise in childhood obesity has made distinguishing between type 1 and type 2 diabetes increasingly more challenging. When to consider a diagnosis of mody at the presentation of. Maturityonset diabetes of the young mody was first reported in 1974 as mild familial diabetes with dominant inheritance. Glucokinasematurityonset diabetes of the young gckmody, also known as mody2, is caused by heterozygous inactivating mutations in the gck gene. We present the case of a male patient with a history of two years of fatigue, mild hyperglycemia and intermittent polyuria, accompanied by a. Mar 30, 2020 maturityonset diabetes of the young mody or monogenic diabetes is an autosomal dominant form of noninsulindependent diabetes that typically presents before the age of 25 years 1. Mody in japanese people are similar to those of other ethnic populations.
Diabetes caused by mutations in the glucokinase gck gene. Description mody is a form of niddm 125853 characterized by monogenic autosomal dominant transmission and. Because glycemia was matched between groups, the presence of iatrogenic hyperinsuline. A gp will often be the first health professional involved in making a diagnosis of diabetes. Gck analysis for maturity onset diabetes of the young. A clinical questionnaire for maturityonset diabetes of the young mody should be submitted with specimens. Gck mody represents about 3% of patients with gestational diabetes 17. Recently 14 genes associated with mody have been proposed and the clinical characteristics differ according to the genetic etiology. Out of fourteen, up to date discovered, mody genes the most often affected ones include gck gene encoding glucokinase enzyme and hnf1a encoding the. At the conclusion of this presentation, participants should be able to. There is limited data about management of gckmody in pregnancy. Gck mody has generally been considered a phenotypically homogenous mild form of diabetes, which does not lead to marked hyperglycemia or diabetes. Maturity onset diabetes of the young mody comprises a heterogeneous group of monogenic disorders characterised by. Copy number variation in gck in patients with maturityonset.
Caudal regression syndrome in a fetus of a glucokinase. Gck mody diabetes associated with protein misfolding, cellular selfassociation and degradation. Atypical hyperglycemia presentation suggests considering a. We studied eight participants with gck mody maturity onset diabetes of young due to heterozygous inactivating mutations of the gck gene, comparing responses with data collected from eight healthy controls and six participants with type 2 diabetes matched for fasting plasma glucose with gck mody participants. Molecular and clinical characterization of glucokinase.
Maturity onset diabetes of the young mody is a monogenic form of diabetes inherited as an autosomal dominant trait. Frontiers hidden modylooking for a needle in a haystack. Jul 08, 2019 mody is a rare condition, accounting for 15% of all cases of diabetes12, and 16% of pediatric cases of diabetes. Biomarkers currently used for the diagnosis of maturityonset. However patients are frequently misclassified as type 1, type 2, or gestational diabetes. Pdf gckmody diabetes associated with protein misfolding. This gene contains the blueprint for an enzyme that is important in for the normal regulation of insulin production. The longterm response to sulfonylurea drugs in mody caused by hnf1a and hnf4a mutations and ndm caused by kcnj11 and abcc8 mutations is an excellent. We undertook the first multicenter genetic study of mody in the portuguese. The second most common cause is gck mody due to heterozygous mutations in the gck gene which impair the glucokinase function through different mechanisms such as enzymatic activity, protein stability, and increased interaction with its receptor. Glucokinase diabetes is one of the familial diabetes types that together are often called mody maturity onset diabetes of the young. If there is a change in the gck gene this means that it works slightly differently so that the blood glucose is reset at a higher level than in people without this change. Maturity onset diabetes of the young mody diabetes uk.
There was statistically significant evidence of genetic heterogeneity, with an estimated 45 to 95% of the 16 families showing linkage to glucokinase. Recognition and management of individuals with hyperglycemia. Demystifying maturityonset diabetes of the young mody kristine m. Optimal management of mody diabetes is highly dependent on the underlying genotype. Although insulin resistance consistently occurs with type 1 diabetes, its predominant driver is uncertain. Generally, gck mody mody2 is benign and nonprogressive and can be managed without medication, or other therapeutic measures, including diet, with the exception of special monitoring during pregnancy 2, 3, 36. Journal of clinical medicine article maturityonset diabetes of the young mody in portugal. If a child does inherit the mutation they will generally go on to develop mody before theyre 25, whatever their. Glucokinase is predominantly expressed in pancreatic beta cells and catalyzes the phosphorylation of glucose to glucose6phosphate. Mody probability calculator for gck and hnf1a screening in. Misdiagnosis as type 1, type 2 or gestational diabetes and the high costs of commercial genetic testing are barriers to acquiring an accurate diagnosis. In latinamerica little information has been described about the frequency of the disease, perhaps due to limited access to genetic studies.
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