ABCC8-Related Maturity-Onset Diabetes of the Young (MODY12): A Report of a Chinese Family

Lin, Leweihua; Quan, Huibiao; Chen, Kaining; Chen, Daoxiong; Lin, Danhong; Fang, Tuanyu

doi:10.3389/fendo.2020.00645

Cited by 14 publications

(12 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MODY12 was first reported by Bowman in 2012 31 . In the reported cases, 32,33 the patients' blood glucose levels were elevated with or without ketosis, and diabetes antibody tests were negative, some of them had decreased C‐peptide levels. Moreover, some patients had retinopathy and urinary proteins.…”

Section: Discussionmentioning

confidence: 98%

“…These findings indicate the heterogeneity of genotype–phenotype correlations in ABCC8 ‐associated diabetes. Sulfonylureas can combine with the sulfonylurea receptor‐1 subunit to close the channel and release insulin, thus MODY12 is sensitive to oral sulfonylurea drugs 32 . In addition, metformin exerts a satisfactory therapeutic effect 34 .…”

Section: Discussionmentioning

confidence: 99%

“…Sulfonylureas can combine with the sulfonylurea receptor-1 subunit to close the channel and release insulin, thus MODY12 is sensitive to oral sulfonylurea drugs. 32 In addition, metformin exerts a satisfactory therapeutic effect. 34 Drugs such as inhibitors of DPP-4 and sodium-glucose cotransporter-2 have been used for treating MODY.…”

Section: F I G U R Ementioning

confidence: 99%

See 2 more Smart Citations

ABCC8 ‐related maturity‐onset diabetes of the young: Clinical features and genetic analysis of one case

Zhou

Sun

et al. 2022

Pediatric Diabetes

View full text Add to dashboard Cite

Objective: To confirm the diagnosis of a 13-year-old adolescent with familial diabetes and further examine his genetic pathogeny.Research Design and Methods: Clinical data were collected, and genetic examination was performed. PolyPhen-2 and Mutation Taster were used to predict the deleterious effects of the variant. Clustal Omega software was used to confirm the conservation of amino acid substitutions. To examine changes in the expression of proteins, recombinant vectors were constructed, and the expression of wild-type and variant target genes was detected through quantitative polymerase chain reaction. Furthermore, the wild-type and variant eukaryotic recombinant vectors were treated with a ubiquitin degradation inhibitor (MG132) and a lysosomal degradation pathway inhibitor (CQ, 3-mA). The expression of target proteins was detected through Western blot analysis. Results:The patient had hyperglycaemia (27 mmol/L), a high HbA1c level (13.1%), a decreased C-peptide level (0.63 ng/ml) and no diabetes antibodies. The patient had a family history of diabetes. The novel variation of ABCC8 c.2477G>A was detected in the proband and his relatives. The mutation was predicted to be harmful. Changes in the protein structure were observed. The ABCC8 c.2477G >A variant resulted in an increase in ABCC8 expression. Furthermore, changes in the expression of the ABCC8 variant was observed after 3-MA treatment, especially after treatment with MG132.At the follow-up, the patient's glucose level was normal without drug therapy for more than 2 years until until he started taking Trelagliptin Succinate to control hyperglycemia within the recent 6 months. Conclusions:The diagnosis of maturity-onset diabetes of the young (MODY)12 was confirmed in our patient. The ABCC8 variant inhibited both ubiquitination and autophagy lysosome degradation pathways, especially the ubiquitination degradation pathway.

show abstract

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

ABCC8 ‐related maturity‐onset diabetes of the young: Clinical features and genetic analysis of one case

Zhou

Sun

et al. 2022

Pediatric Diabetes

View full text Add to dashboard Cite

show abstract

“…The ABCC8 gene, encoding the sulfonylurea receptor 1 subunit of the ATP-sensitive potassium (K ATP ) channel, can regulate the secretion of insulin. ABCC8 mutations have been shown to cause congenital hyperinsulinism (CHI), type 2 DM, gestational DM, neonatal diabetes, and MODY [ 13 ]. CHI is associated with the blindness of pancreatic β-cells responsible for insulin secretion, causing severe and persistent hypoglycemia.…”

Section: Discussionmentioning

confidence: 99%

“…This is the limitation of our case and thus, further validations in additional patients and functional studies are needed to prove the pathogenicity of this variant. Patients with MODY 12 respond to sulfonylurea therapy [ 13 ]. Thus, switching our patient from insulin to sulfonylurea is under consideration.…”

Section: Discussionmentioning

confidence: 99%

Hypertriglyceridemia with acute pancreatitis in a 14-year-old girl with diabetic ketoacidosis

Park¹,

Kim

et al. 2022

Ann Pediatr Endocrinol Metab

View full text Add to dashboard Cite

Diabetic ketoacidosis (DKA) is a medically fatal condition in poorly controlled hyperglycemia or newly diagnosed diabetes mellitus. Severe hypertriglyceridemia (HTG) is an uncommon complication of DKA and can be associated with acute pancreatitis (AP). We present the clinical manifestations, laboratory findings, and management of AP associated with HTG in a 14-year-old girl with DKA. The patient with seven-year history of type 2 diabetes presented with epigastric pain, 1 month after stopping insulin injection. DKA, severe HTG, and AP were diagnosed based on the laboratory and imaging tests. She recovered from DKA after conventional treatment for DKA, and her triglyceride (TG) level was reduced from 10,867 mg/dL to normal range after 6 days of admission without anti-lipid medication.Considering not too low C-peptide levels, negative diabetes-related antibodies and high TG level, targeted gene panel sequencing was performed on the genes associated with diabetes and HTG. We identified a heterozygous mutation c.4607C>T (p. Ala1537Val) in ABCC8 related to maturity-onset diabetes of the young (MODY) 12. This is the first reported case of HTG induced AP with DKA in a patient with MODY. In addition, we reviewed the literatures for pediatric cases of HTG with DKA. In patients with DKA, timely awareness of severe HTG related to insulin deficiency is crucial for improving the consequence of AP. We recommend considering AP in all DKA patients presenting with severe HTG to ensure early and proper management.

show abstract

ABCC8 variants in MODY12: Review of the literature and report of a case with severe complications

Timmers

Dirinck

Lauwers

et al. 2021

Diabetes Metabolism Res

View full text Add to dashboard Cite

More than 1000 variants of the ATP-binding cassette transporter subfamily C member 8 (ABCC8) gene have been reported in neonatal diabetes mellitus. Up to now only 55 ABCC8 variants were associated with Maturity-Onset Diabetes of the Young 12 (MODY12). We present a c.3544C>T p.(Arg1182Trp) ABCC8 variant in a 35-year-old women who had pronounced microvascular diabetic complications and a charcot arthropathy necessitating a lower limb amputation. The unusual severity of the disease course prompted us to perform a systematic review of all genetic variants in MODY12. The present mutation has mostly been associated with neonatal diabetes and in only three papers reporting a MODY12. The 55 MODY12 variants show a large clinical heterogeneity, even in relatives with the same mutation, ranging from mild impaired glucose tolerance to severe insulin-dependent diabetes mellitus. HbA1c at diagnosis ranged from 5% to 14% and age at diagnosis ranged from 2 to 53 years. However, several case reports lack documentation of diabetic complications. Hence, more detailed reports remain necessary to improve insight in MODY12 pathophysiology and outcome. In this article current data regarding therapeutic management are provided, and key points to consider for the individual patient affected by MODY12 are presented.

show abstract

ABCC8-Related Maturity-Onset Diabetes of the Young (MODY12): A Report of a Chinese Family

Cited by 14 publications

References 27 publications

ABCC8 ‐related maturity‐onset diabetes of the young: Clinical features and genetic analysis of one case

ABCC8 ‐related maturity‐onset diabetes of the young: Clinical features and genetic analysis of one case

Hypertriglyceridemia with acute pancreatitis in a 14-year-old girl with diabetic ketoacidosis

ABCC8 variants in MODY12: Review of the literature and report of a case with severe complications

Contact Info

Product

Resources

About