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DEND Syndrome

NDM


Presentation

  • Here, we present the first case of a DEND syndrome-afflicted patient with water intake disorder and increased serum vasopressin level, possibly related to altered KATP channel activity.[ncbi.nlm.nih.gov]
  • 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.[ncbi.nlm.nih.gov]
  • In the present study, we sequenced the KCNJ11 gene in a Chinese boy diagnosed with permanent neonatal diabetes mellitus (PNDM) and also in his parents.[ncbi.nlm.nih.gov]
  • A 50-day-old male presented with fever and seizure, complicated by persistent hyperglycemia. Insulin therapy was initiated. At 10 months of age, the patient was unable to hold his head up and make eye contact with others.[ncbi.nlm.nih.gov]
  • A 50-day-old male presented with fever and seizure, complicated by persistent hyperglycemia...[readbyqxmd.com]
Asymptomatic
  • Only two asymptomatic hypoglycemic episodes were recorded and both quickly resolved with oral glucose. No other side effects were reported.[care.diabetesjournals.org]

Workup

Abnormal Spikes
  • Antiepileptic therapy was discontinued following the absence of an abnormal spike or wave on EEG. However, the patient's psychomotor retardation was not observed to improve.[jkms.org]
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]
Glucose Increased
  • In five patients, the maximum insulin increment in response to oral glucose increased from 7.1 pmol per liter to 53.6 pmol per liter (P 0.04) ( Figure 3A ).[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 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]
  • This case report highlights a case of successful sulfonylurea treatment in a patient with DEND syndrome.[ncbi.nlm.nih.gov]
  • 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[ncbi.nlm.nih.gov]
  • Since then, treatment with gliclazide was initiated and the insulin dose was gradually reduced. Following 3 months, insulin was discontinued with a gliclazide dose of 2.4 mg/kg.[ncbi.nlm.nih.gov]
  • There have been rare cases of juvenile patients with intermediate DEND syndrome (iDEND) reporting variable improvement in neurological function following transition from insulin to SU treatment.[ncbi.nlm.nih.gov]

Prognosis

  • 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]
  • […] eld of pediatric diabetes, in an attempt to determine the most accurate diagnosis and its implications on appropriate treatment and prognosis.[dialnet.unirioja.es]

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]
Sex distribution
Age distribution

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. Prog Biophys Mol Biol 81 : 133 – 176 Shyng SL, Nichols CG ( 1997 ) Octameric stoichiometry of the K ATP channel complex.[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]
  • 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]
  • […] 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]
  • 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]

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