Neonatal Diabetes Mellitus: Novel Mutations

Nayak, Sapna; Sarangi, Aditya Narayan; Sahoo, Saroj Kumar; Mangla, Pragya; Tripathy, Manoranjan; Rao, Sudha; Gupta, Suchit; Paliwal, Vimal Kumar; Sudhanshu, Siddhnath; Ravi, Chaitra; Joshi, Kriti; Bhatia, Vijayalakshmi; Bhatia, Eesh

doi:10.1007/s12098-020-03567-7

Cited by 14 publications

(7 citation statements)

References 25 publications

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“…also collated data of all previously published Indian data on NDM which demonstrates the bulk of all NDM cases to be due to potassium ATP (KATP) channel defects – ABCC8 and then KCNJ11 . [ 18 ] However, WRS from EIF2AK3 mutation still remains the most frequently reported aetiology for permanent neonatal diabetes mellitus (PNDM). This study also describes a unique case of transient NDM with a homozygous ABCC8 mutation.…”

Section: Discussionmentioning

confidence: 99%

Genetic Heterogeneity and Challenges in the Management of Permanent Neonatal Diabetes Mellitus: A Single-Centre Study from South India

Korula

Ravichandran

Paul

et al. 2022

Indian Journal of Endocrinology and Metabolism

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Aim and Objectives: 1. To study the clinical outcome, growth and glycaemic control, 2. To study the frequency and type of genetic mutations. Methods: This is a retrospective study with a review of data of medical records from 2008 till date. Results: Twelve patients (six males) with neonatal diabetes mellitus (NDM) were identified. Median (interquartile range – (IQR)) age at diagnosis was 72 (31–95) days with a history of consanguinity in 75%. The median birth weight (range) was 2345 (900–3300) g. Follow-up data were available for eight patients with a median age at (IQR) follow-up of 3.3 (3–5.3) years. At follow-up, the mean annual HbA1c was 8.2% at a mean insulin dose of 1.1 U/kg/d. One patient with Wolcott-Rallison syndrome (WRS) and 21α-hydroxylase deficiency had poor growth and intellectual difficulty. The rest demonstrated satisfactory growth with an increase of mean weight centile from 2 nd to 13 th , height centile from 6.5 th to 20 th and normal neuro-cognitive development. Eleven patients underwent genetic testing with a molecular diagnosis in 54% (6/11): EIF2AK3 ( n = 2) and one each in INS , PDX1 , IL2RA and FOXP3 . None had variants in ABCC8 or KCNJ11 . One with immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome underwent haematopoietic stem cell transplant (HSCT) and later succumbed. Conclusion: Our study demonstrates good clinical outcomes among NDM patients without immune dysfunction. Molecular diagnosis was attained only in around half of the patients (54%) with a great genetic heterogeneity.

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Section: Discussionmentioning

confidence: 99%

Genetic Heterogeneity and Challenges in the Management of Permanent Neonatal Diabetes Mellitus: A Single-Centre Study from South India

Korula

Ravichandran

Paul

et al. 2022

Indian Journal of Endocrinology and Metabolism

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“…Tables 1 and 2 summarize the important published data on the occurrence of different types of monogenic diabetes in India. [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] Are there regional differences in the way monogenic diabetes presents in India?…”

Section: What Are the Common Forms Of Monogenic Diabetes Seen Among I...mentioning

confidence: 99%

“…Permanent NDM KCNJ11 gene mutation -20 (DEND Syndrome in 3/20) ABCC8 gene mutation -19 33 out of total 39 (84%) patients (KCNJ11+ABCC8) switched to sulfonylurea Nayak et al 2021 [15] 12 infants with NDM 8 presented at <6 months…”

Section: Chennaimentioning

confidence: 99%

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Genetics for the pediatric endocrinologists – 1

Radha

Mohan

Kumar

2022

JPED

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The advancement in genetic laboratory technology has helped immensely in the diagnosis of many genetic disorders which could not hitherto be diagnosed. Monogenic diabetes among children and adolescents is not uncommon and needs a high index of clinical suspicion to diagnose. With the availability of genetic diagnostic laboratories with the latest technology, more and more patients should benefit from early diagnosis, specific targeted treatment, and better outcomes. The pediatricians and pediatric endocrinologists managing children with diabetes need to clinically suspect and advise appropriate genetic tests to confirm the diagnosis of monogenic diabetes. Neonatal diabetes mellitus is one of the most rewarding diagnoses, if we pick up a specific genetic abnormality that could respond to sulfonylurea. The child with KCNJ11 or ABCC8 gene mutation responding to sulfonylurea could escape from the life-long insulin injections and complications of diabetes. It is equally important to identify other forms of monogenic diabetes as the specific diagnosis can have implications in the treatment, genetic counseling, and identifying other family members harboring the same gene mutation.

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“…Heterozygous de novo missense variants in EIF2AK2, the gene that encodes PKR, are associated with the neurodevelopmental disorder Leukoencephalopathy, Developmental Delay, and Episodic Neurologic Regression Wolcott-Rallison syndrome (Abali et al, 2020;Abbasi et al, 2018;Al-Aama et al, 2018;Alkorta-Aranburu et al, 2014;Al-Sinani et al, 2015;Anne et al, 2021;Asl et al, 2019;Behnam et al, 2013;Davoodi et al, 2018;Fatani, 2019;Feng et al, 2011;Furdela et al, 2016;Gürbüz et al, 2016;Habeb et al, 2015;Huang & Wei, 2019;Jahnavi et al, 2014;Julier & Nicolino, 2010;Mihci et al, 2012;Nayak et al, 2021;Reis et al, 2011;Sang et al, 2011;Sümegi et al, 2020;…”

Section: Genetic Diseases Of Eif2ak2 (Pkr)mentioning

confidence: 99%

A (dis)integrated stress response: Genetic diseases of eIF2α regulators

2021

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The integrated stress response (ISR) is a conserved mechanism by which eukaryotic cells remodel gene expression to adapt to intrinsic and extrinsic stressors rapidly and reversibly. The ISR is initiated when stress-activated protein kinases phosphorylate the major translation initiation factor eukaryotic translation initiation factor 2ɑ (eIF2ɑ), which globally suppresses translation initiation activity and permits the selective translation of stress-induced genes including important transcription factors such as activating transcription factor 4 (ATF4). Translationally repressed messenger RNAs (mRNAs) and noncoding RNAs assemble into cytoplasmic RNA-protein granules and polyadenylated RNAs are concomitantly stabilized. Thus, regulated changes in mRNA translation, stability, and localization to RNA-protein granules contribute to the reprogramming of gene expression that defines the ISR. We discuss fundamental mechanisms of RNA regulation during the ISR and provide an overview of a growing class of genetic disorders associated with mutant alleles of key translation factors in the ISR pathway.

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Neonatal Diabetes Mellitus: Novel Mutations

Cited by 14 publications

References 25 publications

Genetic Heterogeneity and Challenges in the Management of Permanent Neonatal Diabetes Mellitus: A Single-Centre Study from South India

Genetic Heterogeneity and Challenges in the Management of Permanent Neonatal Diabetes Mellitus: A Single-Centre Study from South India

Genetics for the pediatric endocrinologists – 1

A (dis)integrated stress response: Genetic diseases of eIF2α regulators

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