Presentation
The most severe clinical form of PNDM presents as Developmental delay, Epilepsy and Neonatal Diabetes (DEND) syndrome. Diagnosis is confirmed by genetic mutation testing. Oral sulfonylurea therapy improves neurological outcome. [unboundmedicine.com]
A 50-day-old male presented with fever and seizure, complicated by persistent hyperglycemia... [readbyqxmd.com]
These patients often present with PNDM with additional features such as liver disease and epiphyseal dysplasia developing later. [diapedia.org]
Entire Body System
- Noncompliance
This is attributed to the characteristic of the specific mutation, to B-cell glucotoxicity from prolonged poor control before transfer, or to noncompliance. 30 In fact, patients should be given a trial of sulfonylurea for a period of at least 3 months [dovepress.com]
Jaw & Teeth
- Tooth Discoloration
Tooth discoloration in patients with neonatal diabetes after transfer onto glibenclamide: a previously unreported side effect. Diabetes Care 2009;32:1428–30. 19. Flanagan SE, Edghill EL, Gloyn AL, Ellard S, Hattersley AT. [e-apem.org]
Despite these relatively high doses, the only side-effects reported include transitory diarrhoea or tooth discoloration in a few patients. [diapedia.org]
Tooth discoloration in patients with neonatal diabetes after transfer onto glibenclamide: a previously unreported side effect. Diabetes Care. 2009;32(8):1428–1430. 54. Iafusco D, Bizzarri C, Cadario F, et al. [dovepress.com]
Urogenital
- Polyuria
Testing is appropriate for: Infants with persistent hyperglycemia ± history of intrauterine growth retardation, osmotic polyuria, severe hydration and failure to thrive. [seattlechildrenslab.testcatalog.org]
The diabetes is usually diagnosed in the first 3 months of life due to continuing poor weight gain, polyuria, or diabetic ketoacidosis. Rare cases have been recognized as late as 6 months of age. [en.wikipedia.org]
At the age of 5 months she developed fever, polyuria, irritability and laboratory work-up revealed glucosuria and a blood glucose level of 900 mg/dL; however, ketoacidosis was not documented. [scielo.br]
Initial clinical manifestations include hyperglycemia, glycosuria, intrauterine growth retardation, osmotic polyuria, severe dehydration, and failure to gain weight. [blueprintgenetics.com]
Workup
EEG
- Spike-and-Slow-Waves
A subsequent electroencephalogram showed slow background activity with multifocal spikes and slow wave complexes and then she was initiated on valproic acid (40 mg/kg/d). [scielo.br]
- Multifocal Spikes
A subsequent electroencephalogram showed slow background activity with multifocal spikes and slow wave complexes and then she was initiated on valproic acid (40 mg/kg/d). [scielo.br]
- Neurophysiologic Abnormalities
The prompt care is clinically important as both hypoglycemia and hyperglycemia are associated with acute neurophysiological abnormalities and later neurodevelopmental impairment. [dovepress.com]
Serum
- Glucose Increased
Panel B shows the median incremental increase in insulin and glucose concentration from baseline in response to intravenous glucose, oral glucose, and a mixed meal in seven patients whose treatment was successfully switched from insulin to sulfonylurea [nejm.org]
- Amino Acids Increased
In this regard, Trapp and cols. (31) demonstrated experimentally that mutations at residue 166 that replace cysteine – an hydrophobic amino acid, by larger and less hydrophobic amino acids increased the channel open probability, suggesting that the altered [scielo.br]
Treatment
The other 2 patients have no reaction to medical treatment and continuing with insulin treatment. [omicsonline.org]
Glucose and C-peptide responses stimulated by oral glucose tolerance test (OGTT), hemoglobin A1c levels, the 8-point self-measured blood glucose (SMBG) profile and the frequency of hypoglycemia episodes were analyzed, before and during treatment with [discovery.dundee.ac.uk]
The aim of this study was to determine the clinical effects, functional cause, and sensitivity to sulfonylurea treatment of a novel KCNJ11 mutation producing DEND syndrome. [ncbi.nlm.nih.gov]
Parents and patients should understand that the risk of hypo- and hyperglycemia exists on sulfonylurea treatment, and education in their prevention and treatment should be given. [dovepress.com]
Sulfonylurea treatment in permanent neonatal diabetes due to G53D mutation in the KCNJ11 gene: improvement in glycemic control and neurological function. Diabetes Care. 2007;30:e108. [ Links ] 23. [scielo.br]
Prognosis
[…] eld of pediatric diabetes, in an attempt to determine the most accurate diagnosis and its implications on appropriate treatment and prognosis. [dialnet.unirioja.es]
Furthermore, glyburide may improve the neurologic prognosis, by decreasing not only the number of hypoglycemia events, but also by restoring K ATP channel function in neuronal cells. [care.diabetesjournals.org]
Etiology
Etiology DEND syndrome is caused in most cases by gain of channel function mutations in the KCNJ11 gene (11p15.1), encoding a subunit of the ATP-sensitive potassium (KATP) channel. [orpha.net]
Although neonatal diabetes is a common outcome, the severity of symptoms and other associated features are dependent on the underlying genetic etiology. [dovepress.com]
Our aim was to consider a possible monogenic etiology in a 12-yr-old boy with early onset diabetes and mild neurological features. [readbyqxmd.com]
Epidemiology
Summary Epidemiology Fewer than 40 cases have been reported to date. Clinical description DEND syndrome represents the most severe end of the neonatal diabetes mellitus spectrum. [orpha.net]
Permanent neonatal diabetes mellitus: clinical presentation and epidemiology in Oman. Arch Dis Child Fetal Neonatal Ed. 1999;80:F209–12. PubMedCentral PubMed CrossRef Google Scholar 5. [link.springer.com]
[…] collaborate analysis of diabetic criteria in AsiaDECODA研究 Diabetes epidemiology collaborate analysis of diabetic criteria in EuropeDECODE研究 Diabetes epidemiology research internationalDERI研究 Diabetes mellitus due to other specific mechanisms or disease [jds.or.jp]
Pathophysiology
Genetics and pathophysiology of neonatal diabetes mellitus. J Diabetes Investig 2011;2:158–69. 2. Gloyn AL, Pearson ER, Antcliff JF, Proks P, Bruining GJ, Slingerland AS, et al. [e-apem.org]
J Mol Biol 234 : 779 – 815 ↵ Seino S, Miki T ( 2003 ) Physiological and pathophysiological roles of ATP‐sensitive K + channels. [embor.embopress.org]
Prevention
Sulfonylureas improve K ATP channel function in the pancreatic β-cell and also in neuronal and muscle cells, and could potentially play a role in the treatment and/or prevention of such neurologic manifestations. [care.diabetesjournals.org]
[…] programDPP試験 Diabetes prevention trial-1DPT-1試験 Diabetes prevention trial-Type 1DPT-1試験 Diabetic nephropathy remission and regression team trial in JapanDNETT-Japan Diabetic retinopathy candesartan trialsDIRECT試験 Donohue's syndromeドナヒュー症候群 Duloxetine [jds.or.jp]
Functional studies have demonstrated that these ABCC8 and KCNJ11 mutations cause diabetes by reducing the sensitivity of the K-ATP channel to ATP thereby preventing insulin secretion. [diapedia.org]
Parents and patients should understand that the risk of hypo- and hyperglycemia exists on sulfonylurea treatment, and education in their prevention and treatment should be given. [dovepress.com]
This hyperpolarization keeps voltage-gated calcium channels closed, preventing calcium influx and insulin release. Other stimuli, such as GLP1, are ineffective because the membrane is hyperpolarized and cytosolic calcium levels remain low. [nejm.org]