scholarly journals Maturity Onset Diabetes of the Young Masquerading as New Onset Diabetes Mellitus Type 1

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A391-A392
Author(s):  
Assia Miller ◽  
Renee Bargman
Keyword(s):  
Total Daily Dose ◽  
Oral Glucose ◽  
Maturity Onset Diabetes ◽  
Gad Antibodies ◽  
Presumptive Diagnosis ◽  
Hb A1c ◽  
Onset Diabetes ◽  
Gad 65 ◽  
Work Up

Abstract Introduction:/background: Maturity-onset diabetes of the young (MODY) is a heterogeneous group of monogenic disorders with autosomal dominant mode of inheritance. Mutation in hepatocyte nuclear factor-1β (HNF-1β) gene results in an error of embryonic development of pancreas and nephron, leading to MODY type 5. MODY 5 accounts for 1% of maturity-onset diabetes of the young. It has peak incidence in adolescence/early adulthood, and is associated with renal pathology. Clinical Case: A 15-year boy with history of hypertension and Hashimoto thyroiditis with normal thyroid function was referred for Hb A1C of 6.7% (< 6.4%). Physical exam was remarkable for normal weight at 64%, normal BMI at 83%, absence of thyromegaly or acanthosis nigricans. Diabetes was confirmed by 2 hour Oral Glucose Tolerance Test study (baseline glucose 154 mg/dL (<126 mg/dL), 2 hour glucose 384 mg/dL (<140 mg/dL)). Small doses of insulin (total daily dose 0.1 units/kg/day) resulted in good glucose control. Further labs were significant for weakly positive TTG and GAD antibodies (tTG Ab IgA 55.5 U/mL (<4.0 U/mL), GAD-65 Ab 0.05 nmol/L (< 0.02 nmol/L)), positive TPO (0.0 - 34.9 IU/mL) and detectable ATA antibodies 45.8 IU/mL (0.0 - 40.0 IU/mL), C-peptide 2.9 ng/mL (0.9–7.1 ng/mL). Islet cell, Insulin and Zinc transporter 8 antibodies were negative. Over the next few months he was weaned off insulin and subsequently he had a high insulin of 29.43 uU/mL (3.0 - 17.0 uU/mL) with glucose level of 169 mg/dL. Renal US was performed as part of the work up for hypertension and revealed a small right calculus with no hydronephrosis and a small 8-mm cortical cyst in the right kidney. Urinalysis showed microalbuminuria. Upper GI endoscopy and colonoscopy with biopsy ruled out celiac disease. Presumptive diagnosis of MODY was entertained despite positive TPO, ATA, TTG and GAD antibodies suggesting autoimmune endocrinopathies. His Hb A1C levels were in the range of 5.7 to 6 % during the 15 months of follow up. Genetic testing for MODY resulted in heterozygous deletion of exons 1–9 of the HNF1B gene consistent with MODY5. Conclusion: This is a case of MODY 5 with weakly positive GAD 65 antibodies that was initially misdiagnosed as type 1 diabetes. The presence of weakly positive antibodies should not preclude a work up for MODY in a patient who does not have the clinical features of classic type 1 DM.

scholarly journals Maturity Onset Diabetes of the Young due to Glucokinase, HNF1-A, HNF1-B, and HNF4-A Mutations in a Cohort of Turkish Children Diagnosed as Type 1 Diabetes Mellitus

2018 ◽  
Vol 90 (4) ◽  
pp. 257-265 ◽  
Author(s):  
Elif Ozsu ◽  
Filiz Mine Cizmecioglu ◽  
Gul Yesiltepe Mutlu ◽  
Aysegul Bute Yuksel ◽  
Mursel Calıskan ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Rare Condition ◽  
High Sensitivity ◽  
Genetic Mutation ◽  
Nuclear Factor ◽  
Maturity Onset Diabetes ◽  
Hepatocyte Nuclear Factor ◽  
Turkish Children ◽  
Onset Diabetes

Background/Aims: Maturity onset diabetes of the young (MODY) is a rare condition often misdiagnosed as type 1 diabetes (T1D). The purposes of this study were: to identify any patients followed in a large Turkish cohort as T1D, with an atypical natural history, who may in fact have MODY, and to define the criteria which would indicate patients with likely MODY as early as possible after presentation to allow prompt genetic testing. Methods: Urinary C-peptide/creatinine ratio (UCPCR) was studied in 152 patients having a diagnosis of T1D for at least 3 years. Those with a UCPCR ≥0.2 nmol/mmol were selected for genetic analysis of the Glucokinase (GCK), Hepatocyte nuclear factor 1a (HNF1A), Hepatocyte nuclear factor 4a (HNF4A), and Hepatocyte nuclear factor 1b (HNF1B) genes. This UCPCR cut-off was used because of the reported high sensitivity and specificity. Cases were also evaluated using a MODY probability calculator. Results: Twenty-three patients from 152 participants (15.1%) had a UCPCR indicating persistent insulin reserve. The mean age ± SD of the patients was 13.6 ± 3.6 years (range 8.30–21.6). Of these 23, two (8.7%) were found to have a mutation, one with HNF4A and one with HNF1B mutation. No mutations were detected in the GCK or HNF1A genes. Conclusion: In Turkish children with a diagnosis of T1D but who have persistent insulin reserve 3 years after diagnosis, up to 9% may have a genetic mutation indicating a diagnosis of MODY.

Maturity-Onset Diabetes of the Young (MODY): Genetic Causes, Clinical Characteristics, Considerations for Testing, and Treatment Options

Endocrines ◽  
2021 ◽  
Vol 2 (4) ◽  
pp. 485-501
Author(s):  
Zoltan Antal
Keyword(s):  
Clinical Presentation ◽  
Clinical Symptoms ◽  
Treatment Options ◽  
Maturity Onset Diabetes ◽  
Onset Diabetes ◽  
Inappropriate Treatment ◽  
Monogenic Forms Of Diabetes ◽  
Initial Description

Maturity Onset Diabetes of the Young (MODY) encompasses a group of rare monogenic forms of diabetes distinct in etiology and clinical presentation from the more common forms of Type 1 (autoimmune) and Type 2 diabetes. Since its initial description as a clinical entity nearly 50 years ago, the underlying genetic basis for the various forms of MODY has been increasingly better elucidated. Clinically, the diagnosis may be made in childhood or young adulthood and can present as overt hyperglycemia requiring insulin therapy or as a subtle form of slowly progressive glucose impairment. Due to the heterogeneity of clinical symptoms, patients with MODY may be misdiagnosed as possessing another form of diabetes, resulting in potentially inappropriate treatment and delays in screening of affected family members and associated comorbidities. In this review, we highlight the various known genetic mutations associated with MODY, clinical presentation, indications for testing, and the treatment options available.

Maturity onset diabetes of youth (MODY) in Turkish children: sequence analysis of 11 causative genes by next generation sequencing

2016 ◽  
Vol 29 (4) ◽  
Author(s):  
Sebahat Yılmaz Ağladıoğlu ◽  
Zehra Aycan ◽  
Semra Çetinkaya ◽  
Veysel Nijat Baş ◽  
Aşan Önder ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Next Generation Sequencing ◽  
Point Mutations ◽  
Maturity Onset Diabetes ◽  
Turkish Children ◽  
Onset Diabetes ◽  
Molecular Studies ◽  
Generation Sequencing

AbstractMaturity-onset diabetes of the youth (MODY), is a genetically and clinically heterogeneous group of diseasesand is often misdiagnosed as type 1 or type 2 diabetes. The aim of this study is to investigate both novel and proven mutations of 11A panel of 11We identified 28 (65%) point mutations among 43 patients. Eighteen patients haveThis is the first study including molecular studies of 11

Genetic and clinical characterisation of maturity-onset diabetes of the young in Spanish families

2000 ◽  
pp. 380-386 ◽  
Author(s):  
A Costa ◽  
M Bescos ◽  
G Velho ◽  
J Chevre ◽  
J Vidal ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Sequencing Analysis ◽  
Model Assessment ◽  
Maturity Onset Diabetes ◽  
Phenotypic Differences ◽  
Glucose Levels ◽  
Onset Diabetes

OBJECTIVE: To investigate the frequencies of the major maturity-onset diabetes of the young (MODY) subtypes in a panel of Spanish families and to assess phenotypic differences in patients with the different subtypes of MODY. METHODS: Forty-eight subjects from twenty families with clinical diagnosis of MODY were studied. They underwent a standardised clinical examination and a 75-g oral glucose tolerance test (OGTT) was performed. Estimations of insulin sensitivity (%S) and insulin secretion capacity (%B) were calculated by the computer-solved homeostasis model assessment (HOMA). Mutations in the coding regions of hepatocyte nuclear factor (HNF)-4alpha/MODY1, glucokinase (GCK/MODY2) and HNF-1alpha/MODY3 genes were investigated by single strand comformation polymorphism and sequencing analysis. RESULTS: Mutations in the GCK and HNF-1alpha genes were observed in 5 (25%) and 7 (35%) families respectively. Novel mutations included R385X, M238fsdelT, V226fsdelTinsAA and S418-7del11 in the GCK gene, and S121fsdelC, V133M, R159Q and V259D in the HNF-1alpha gene. No MODY1 families were found. Subjects which were neither MODY2 nor MODY3 (MODY-X) had a higher fasting glucose than subjects in the other groups. Insulin secretion capacity was similar in the three groups and the insulin sensitivity was decreased in MODY-X subjects. Glucose levels were significantly higher and insulin levels significantly lower, throughout the OGTT, in MODY3 compared with MODY2 subjects. CONCLUSIONS: Mutations in the GCK/MODY2 and HNF-1alpha/MODY3 genes account for the majority of cases in a panel of Spanish MODY families, with MODY3 being the most frequent subtype. The relative frequencies and the clinical characteristics of these MODY subtypes are in agreement with data previously reported in other European populations. MODY-X patients seem to present a heterogeneous clinical profile.

scholarly journals Case Report: A Novel ABCC8 Variant in a Chinese Pedigree of Maturity-Onset Diabetes of the Young

2021 ◽  
Vol 12 ◽  
Author(s):  
Chaoyan Tang ◽  
Liheng Meng ◽  
Ping Zhang ◽  
Xinghuan Liang ◽  
Chaozhi Dang ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Glucose Homeostasis ◽  
Fasting Blood Glucose ◽  
Family Members ◽  
Missense Variant ◽  
Postprandial Blood Glucose ◽  
Chinese Family ◽  
Oral Glucose ◽  
Maturity Onset Diabetes ◽  
Onset Diabetes

BackgroundWe aimed to analyze a novel ABCC8 variant of a Chinese patient with suspected maturity-onset diabetes of the young (MODY) and to provide evidence for precise diagnosis and appropriate treatment.MethodA Chinese family with suspected MODY was recruited in this study, which included a 15-year-old female patient with diabetes. Clinical data and blood samples were collected from the proband and other family members. All of the living relatives were given an oral glucose tolerance test. Next-generation sequencing was performed to identify the mutated genes in the proband. Sanger sequencing was utilized to confirm the location of the pathogenic variant in all subjects. Further treatment was referred to targeted family members according to genetic testing.ResultsThe proband was found to have a random blood glucose level of 244.8 mg/dl and an HbA1c level of 9.2%. Before this investigation, her grandparents had been diagnosed with diabetes. The second uncle, two aunts, mother, and cousin of the proband were diagnosed with diabetes by abnormal HbA1C (6.5–12.1%) and fasting blood glucose (FBG, 91.4–189.7 mg/dl). The second aunt of the proband had impaired glucose homeostasis (HbA1C = 6.4% and FBG = 88.0 mg/dl). One novel missense variant c.1432G>A (p.A478T) in exon 9 of the ABCC8 gene was detected in the proband with suspected MODY. The variant was also found in six family members with diabetes or impaired glucose homeostasis, including her second uncle, two aunts, mother, and cousin. After the treatment was switched to glimepiride, the fasting blood glucose was adjusted to 99.54 mg/dl, the 2-h postprandial blood glucose was 153.54 mg/dl, serum fructosamine was 259 μmol/l, and HbA1c was 5.8%. The glycemic control remained optimal, and no hypoglycemic episodes were observed in the living relatives.ConclusionThis study revealed one novel missense variant of the ABCC8 gene in Chinese families. The present findings indicated that the members of this family responded to treatment with sulfonylureas as previously seen in ABCC8 MODY.

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