Genetic and clinical characteristics of Korean maturity-onset diabetes of the young (MODY) patients

Hwang, Jin Soon; Shin, Choong Ho; Yang, Sei Won; Jung, Sang Won; Huh, Nam

doi:10.1016/j.diabres.2006.03.002

Cited by 61 publications

(66 citation statements)

References 24 publications

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“…GCK gene mutations have been described in other ethnic groups, but studies in this area are limited (33,34). The phenotype of GCK-MODY in far Eastern and South Asian populations appears similar to that seen in the U.K. population (35)(36)(37)(38)(39). There is no reason to suspect a different prevalence of GCK-MODY in non-European populations, though the differentiation from other forms of diabetes may be different given the higher prevalence of type 2 diabetes, particularly in black and South Asian populations (33)(34)(35)(36)(37)(38).…”

Section: Prevalence Of Gck-mody In Modymentioning

confidence: 99%

Recognition and Management of Individuals With Hyperglycemia Because of a Heterozygous Glucokinase Mutation

et al. 2015

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Glucokinase–maturity-onset diabetes of the young (GCK-MODY), also known as MODY2, is caused by heterozygous inactivating mutations in the GCK gene. GCK gene mutations are present in ∼1 in 1,000 of the population, but most are not diagnosed. They are common causes of MODY (10–60%): persistent incidental childhood hyperglycemia (10–60%) and gestational diabetes mellitus (1–2%). GCK-MODY has a unique pathophysiology and clinical characteristics, so it is best considered as a discrete genetic subgroup. People with GCK-MODY have a defect in glucose sensing; hence, glucose homeostasis is maintained at a higher set point resulting in mild, asymptomatic fasting hyperglycemia (5.4–8.3 mmol/L, HbA1c range 5.8–7.6% [40–60 mmol/mol]), which is present from birth and shows slight deterioration with age. Even after 50 years of mild hyperglycemia, people with GCK-MODY do not develop significant microvascular complications, and the prevalence of macrovascular complications is probably similar to that in the general population. Treatment is not recommended outside pregnancy because glucose-lowering therapy is ineffective in people with GCK-MODY and there is a lack of long-term complications. In pregnancy, fetal growth is primarily determined by whether the fetus inherits the GCK gene mutation from their mother. Insulin treatment of the mother is only appropriate when increased fetal abdominal growth on scanning suggests the fetus is unaffected. The impact on outcome of maternal insulin treatment is limited owing to the difficulty in altering maternal glycemia in these patients. Making the diagnosis of GCK-MODY through genetic testing is essential to avoid unnecessary treatment and investigations, especially when patients are misdiagnosed with type 1 or type 2 diabetes.

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Section: Prevalence Of Gck-mody In Modymentioning

confidence: 99%

Recognition and Management of Individuals With Hyperglycemia Because of a Heterozygous Glucokinase Mutation

et al. 2015

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“…However, it has been reported that GCK gene mutations are rare in the Japanese; this was according to the studies that mainly examined adult subjects where there were few reports of GCK mutations in Japanese diabetic patients [7,8]. Similarly, the incidence of GCK gene defects has been reported to be rather low among MODY patients in other Asian countries [9,10].…”

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confidence: 95%

Detection of glucokinase gene defects in non-obese Japanese children diagnosed with diabetes by school medical examinations

et al. 2011

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“…Although the functional effects of these two mutations on GCK enzymatic activity have not been directly studied, the p.Arg191Trp mutation have been identified in French, Japanese, Norwegian, and Korean patients with the MODY2 phenotype (20,(27)(28)(29). p.Glu221Lys mutation was associated with MODY 2 in Italian subjects (30).…”

Section: Discussionmentioning

confidence: 99%

Incidental mild hyperglycemia in children: two MODY 2 families identified in Brazilian subjects

Caetano

Jorge

Malaquias

et al. 2012

Arq Bras Endocrinol Metab

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SUMMARYMaturity-onset diabetes of the young (MODY) is characterized by an autosomal dominant mode of inheritance, early onset of hyperglycemia, and defects of insulin secretion. MODY subtypes described present genetic, metabolic, and clinical differences. MODY 2 is characterized by mild asymptomatic fasting hyperglycemia, and rarely requires pharmacological treatment. Hence, precise diagnosis of MODY is important for determining management and prognosis. We report two heterozygous GCK mutations identified during the investigation of short stature. Case 1: a prepubertal 14-year-old boy was evaluated for constitutional delay of growth and puberty. During follow-up, he showed abnormal fasting glucose (113 mg/dL), increased level of HbA1c (6.6%), and negative β-cell antibodies. His father and two siblings also had slightly elevated blood glucose levels. The mother had normal glycemia. A GCK heterozygous missense mutation, p.Arg191Trp, was identified in the proband. Eighteen family members were screened for this mutation, and 11 had the mutation in heterozygous state. Case 2: a 4-year-old boy investigated for short stature revealed no other laboratorial alterations than elevated glycemia (118 mg/dL); β-cell antibodies were negative. His father, a paternal aunt, and the paternal grandmother also had slightly elevated glycemia, whereas his mother had normal glycemia. A GCK heterozygous missense mutation, p.Glu221Lys, was identified in the index patient and in four family members. All affected patients had mild elevated glycemia. Individuals with normal glycemia did not harbor mutations. GCK mutation screening should be considered in patients with chronic mild early-onset hyperglycemia, family history of impaired glycemia, and negative β-cell antibodies. Arq Bras Endocrinol Metab. 2012;56(8):519-24 SUMÁRIO O diabetes do tipo MODY (maturity-onset diabetes of the young) caracteriza-se por herança autossômica dominante, início precoce da hiperglicemia e defeitos na secreção de insulina. Os subtipos de MODY apresentam diferenças genéticas, metabólicas e clínicas. O MODY 2 é caracterizado por hiperglicemia leve assintomática e raramente requer tratamento farmacológico. O diagnóstico preciso de MODY é importante para se determinar o tratamento e o prognóstico. Relatamos duas mutações no gene GCK em heterozigose identificadas durante investigação de baixa estatura. Caso 1: paciente do sexo masculino, com 14 anos, pré-púbere, avaliado por atraso constitucional do crescimento e da puberdade. Durante o acompanhamento, apresentou glicemia de jejum alterada (113 mg/dL), aumento de HbA1c (6,6%) e anticorpos anticélulas β negativos. Seu pai e dois irmãos também apresentavam glicemia levemente elevada. A mãe tinha glicemia normal. Foi identificada no gene GCK uma mutação missense em heterozigose, p.Arg191Trp. Dezoito membros da família foram rastreados e 11 apresentavam essa mutação. Caso 2: paciente do sexo masculino, com 4 anos, em avaliação por baixa estatura. Não apresentou alterações laboratoriais, exceto por glicemia elevada ...

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Genetic and clinical characteristics of Korean maturity-onset diabetes of the young (MODY) patients

Cited by 61 publications

References 24 publications

Recognition and Management of Individuals With Hyperglycemia Because of a Heterozygous Glucokinase Mutation

Recognition and Management of Individuals With Hyperglycemia Because of a Heterozygous Glucokinase Mutation

Detection of glucokinase gene defects in non-obese Japanese children diagnosed with diabetes by school medical examinations

Incidental mild hyperglycemia in children: two MODY 2 families identified in Brazilian subjects

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