The personalized approach to neonatal diabetes therapy depending on the genetic defect

2017 ◽  
Vol 1 (1) ◽  
pp. 36-39 ◽  
Author(s):  
Yulia V. Tikhonovich ◽  
Natalia A. Zubkova ◽  
Anatoly N. Tiulpakov
Keyword(s):  
Katp Channel ◽  
Genetic Disorders ◽  
Genetic Defect ◽  
Clinical Importance ◽  
Neonatal Diabetes ◽  
Diabetes Treatment ◽  
Diabetes Therapy ◽  
Common Causes ◽  
Genetic Examination ◽  
Personalized Approach

Neonatal diabetes mellitus (NDM) is defined as a heterogeneous group of genetic disorders with onset before 6 months of age. Mutations in KATP channel genes (KCNJ11, ABCC8) and the insulin gene (INS) are the most common causes of NDM. Accurate molecular diagnosis of NDM has significant clinical importance as it may influence diabetes treatment, explain pleiotropic features and define the prognosis in the examined subject as well as in other family members . In this report we present the results of a genetic examination of 70 patients with NDM, generalized the experience of using sulfonylurea in patients with KCNJ11 and ABCC8 genes mutations for the period from 2009 to 2016. A correlation is shown between the type of mutation, the course of the disease, and the sensitivity of patients to glibenclamide.

Intellectual disability in KATP channel neonatal diabetes

2020 ◽  
Author(s):  
Svalastoga P ◽  
Sulen A ◽  
Fehn JR ◽  
Aukland SM ◽  
Irgens H ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Katp Channel ◽  
Neonatal Diabetes

Algorithm for the diagnosis of breathing disorders during sleep in children with neurological pathology

2021 ◽  
Vol 2 (2) ◽  
pp. 73-82
Author(s):  
Vladislav V. Lebedev ◽  
Olga V. Kozhevnikova ◽  
Andrey A. Gazaryan ◽  
Victoriya A. Aysina ◽  
Eka A. Abashidze ◽  
...  
Keyword(s):  
Sleep Disorders ◽  
Neurological Diseases ◽  
Respiratory Disorders ◽  
National Medical ◽  
Sleep Breathing Disorders ◽  
Breathing Disorders ◽  
Common Causes ◽  
Personalized Approach ◽  
Neurological Pathology

Introduction. Sleep disorders in children with nervous system pathology are more pronounced than in the general population. One of the most common causes of sleep disorders in children is sleep-disordered breathing. The aim of our study was to create an algorithm for the diagnosis of sleep breathing disorders in children with neurological pathology. Materials and methods. The results of night studies (160 polysomnographies, 98 cardiorespiratory monitorings) carried out in the department of instrumental diagnostics at the National Medical Research Center for Children’s Health in 258 children (154 boys and 104 girls, aged one month to 17 years) with neurological pathology were analyzed. Questionnaires were used to assess the quality of sleep. An essential criterion for dividing children into groups was the presence of maxillofacial anomalies (MFA). The results were compared with complaints according to questionnaires, age, BMI and ENT-status of patients. Results. In the general sample, a significant (p < 0.001) relationship between respiratory disorders and complaints and the presence of ENT pathology was obtained. The most severe breathing disorders were recorded in children with MFA (p < 0.001). The result was the creation of an algorithm for examining children with neurological pathology. Conclusion. Children with neurological pathology in sleep-breathing disorders require a personalized approach to correcting the causes of these disturbances, depending on the nosology. Chronic pathology of the ENT organs aggravates respiratory disorders during sleep. Regular monitoring of sleep disorders using questionnaires should be included in the algorithm for managing children with neurological diseases of all ages for early detection of these disorders.

scholarly journals Duplication 6q24: More Than Just Diabetes

2020 ◽  
Vol 4 (5) ◽  
Author(s):  
Rachel H Gore ◽  
Maria Eleni Nikita ◽  
Paula G Newton ◽  
Rebecca G Carter ◽  
Jeanine Reyes-Bautista ◽  
...  
Keyword(s):  
Chromosomal Abnormalities ◽  
Uniparental Disomy ◽  
Clinical Importance ◽  
Neonatal Diabetes ◽  
Increased Risk ◽  
Chromosome 6Q24 ◽  
History Of ◽  
Transient Neonatal Diabetes ◽  
Neonatal Hyperglycemia ◽  
Methylation Patterns

Abstract Chromosome 6q24-related transient neonatal diabetes mellitus is characterized by intrauterine growth restriction and low birth weight, with neonatal hyperglycemia resolving by 18 months and an increased risk for type 2 diabetes in adulthood. Molecularly, it is caused by overexpression of the 6q24 imprinted chromosomal region due to a duplication, uniparental disomy, or abnormal methylation. Conventional testing for this condition analyzes methylation patterns at the 6q24 locus but does not evaluate for the presence of other surrounding chromosomal abnormalities. We report a female with a history of neonatal hyperglycemia due to a paternally inherited duplication at chromosomal location 6q24. She subsequently presented to the pediatric genetics clinic at 15 months of age with developmental delay and abnormal balance. Microarray analysis identified a larger 14 Mb chromosomal duplication from 6q24 to 6q25.2, consistent with a diagnosis of duplication 6q syndrome. This case highlights the clinical importance of pursuing further genetic evaluation in patients diagnosed with chromosome 6q24-related neonatal hyperglycemia via targeted methylation-specific multiplex ligation-dependent probe amplification analysis identifying a duplication in this region. Early identification and intervention can improve developmental outcomes for patients with larger chromosome 6q duplications.

Etiology and Management of Pharyngitis and Pharyngotonsillitis in Children: A Current Review

1992 ◽  
Vol 101 (1_suppl) ◽  
pp. 51-57 ◽  
Author(s):  
Jack L. Paradise
Keyword(s):  
Early Treatment ◽  
Clinical Importance ◽  
Hemolytic Streptococcus ◽  
Delayed Treatment ◽  
Current Review ◽  
Common Causes ◽  
Group A ◽  
Penicillin Treatment ◽  
Methods Of Treatment ◽  
A Current

Although viruses are the most common causes of childhood throat infections, interest in the etiology of these infections has primarily focused on whether an individual episode is caused by group A β-hemolytic streptococcus (GABHS), particularly since the recent outbreaks of rheumatic fever in certain areas of the country. Penicillin remains the cornerstone of treatment in GABHS pharyngitis. Early treatment effects prompt clinical improvement and reduces the risk of transmission. Whether early treatment suppresses immunologic response and results in a higher recurrence rate than does delayed treatment is still unknown, but recent evidence suggests that it does not. The causes of persistent GABHS carriage, its clinical importance, and optimal methods of treatment are all still in question. When penicillin treatment does not eradicate carriage, other drugs may be efficacious. In children severely affected with recurrent throat infection, tonsillectomy is generally effective and is sometimes a desirable option.

scholarly journals Diabetes induced by gain-of-function mutations in the Kir6.1 subunit of the KATP channel

2016 ◽  
Vol 149 (1) ◽  
pp. 75-84 ◽  
Author(s):  
Maria S. Remedi ◽  
Jonathan B. Friedman ◽  
Colin G. Nichols
Keyword(s):  
Insulin Secretion ◽  
Katp Channel ◽  
Vascular System ◽  
Wild Type Mouse ◽  
Neonatal Diabetes ◽  
Katp Channels ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Gain Of Function ◽  
Insulin Promoter

Gain-of-function (GOF) mutations in the pore-forming (Kir6.2) and regulatory (SUR1) subunits of KATP channels have been identified as the most common cause of human neonatal diabetes mellitus. The critical effect of these mutations is confirmed in mice expressing Kir6.2-GOF mutations in pancreatic β cells. A second KATP channel pore-forming subunit, Kir6.1, was originally cloned from the pancreas. Although the prominence of this subunit in the vascular system is well documented, a potential role in pancreatic β cells has not been considered. Here, we show that mice expressing Kir6.1-GOF mutations (Kir6.1[G343D] or Kir6.1[G343D,Q53R]) in pancreatic β cells (under rat-insulin-promoter [Rip] control) develop glucose intolerance and diabetes caused by reduced insulin secretion. We also generated transgenic mice in which a bacterial artificial chromosome (BAC) containing Kir6.1[G343D] is incorporated such that the transgene is only expressed in tissues where Kir6.1 is normally present. Strikingly, BAC-Kir6.1[G343D] mice also show impaired glucose tolerance, as well as reduced glucose- and sulfonylurea-dependent insulin secretion. However, the response to K+ depolarization is intact in Kir6.1-GOF mice compared with control islets. The presence of native Kir6.1 transcripts was demonstrated in both human and wild-type mouse islets using quantitative real-time PCR. Together, these results implicate the incorporation of native Kir6.1 subunits into pancreatic KATP channels and a contributory role for these subunits in the control of insulin secretion.

scholarly journals Muscle Dysfunction Caused by a KATP Channel Mutation in Neonatal Diabetes Is Neuronal in Origin

Science ◽  
2010 ◽  
Vol 329 (5990) ◽  
pp. 458-461 ◽  
Author(s):  
R. H. Clark ◽  
J. S. McTaggart ◽  
R. Webster ◽  
R. Mannikko ◽  
M. Iberl ◽  
...  
Keyword(s):  
Katp Channel ◽  
Neonatal Diabetes ◽  
Muscle Dysfunction ◽  
Channel Mutation

scholarly journals Genetic disorders in the GH–IGF-I axis in mouse and man

2007 ◽  
Vol 157 (suppl_1) ◽  
pp. S15-S26 ◽  
Author(s):  
M J E Walenkamp ◽  
J M Wit
Keyword(s):  
Short Stature ◽  
Genetic Disorders ◽  
Genetic Defect ◽  
Postnatal Growth ◽  
Genetic Defects ◽  
Animal Data ◽  
Organ Systems ◽  
Number Of Patients ◽  
Igf I ◽  
And Function

Animal knockout experiments have offered the opportunity to study genes that play a role in growth and development. In the last few years, reports of patients with genetic defects in GH–IGF-I axis have greatly increased our knowledge of genetically determined causes of short stature. We will present the animal data and human reports of genetic disorders in the GH–IGF-I axis in order to describe the role of the GH–IGF-I axis in intrauterine and postnatal growth. In addition, the effects of the GH–IGF-I axis on the development and function of different organ systems such as brain, inner ear, eye, skeleton, glucose homeostasis, gonadal function, and immune system will be discussed. The number of patients with genetic defects in the GH–IGF-I axis is small, and a systematic diagnostic approach and selective genetic analysis in a patient with short stature are essential to identify more patients. Finally, the implications of a genetic defect in the GH–IGF-I axis for the patient and the therapeutic options will be discussed.

scholarly journals Mutations in C11ORF70 cause primary ciliary dyskinesia with randomization of left/right body asymmetry due to outer and inner dynein arm defects

2017 ◽  
Author(s):  
Inga M. Höben ◽  
Rim Hjeij ◽  
Heike Olbrich ◽  
Gerard W. Dougherty ◽  
Tabea Menchen ◽  
...  
Keyword(s):  
Male Infertility ◽  
Primary Ciliary Dyskinesia ◽  
Genetic Defect ◽  
Clinical Importance ◽  
Airway Disease ◽  
Cytoplasmic Dynein ◽  
Loss Of Function ◽  
Reading Frame ◽  
Dynein Arms ◽  
Ciliary Dyskinesia

AbstractPrimary ciliary dyskinesia (PCD) is characterized by chronic airway disease, male infertility and randomization of the left/right body axis caused by defects of motile cilia and sperm flagella. We identified loss-of-function mutations in the open reading frame C11ORF70 in PCD individuals from five distinct families. Transmission electron microscopy analyses and high resolution immunofluorescence microscopy demonstrate that loss-of-function mutations in C11ORF70 cause immotility of respiratory cilia and sperm flagella, respectively, due to loss of axonemal outer (ODAs) and inner dynein arms (IDAs), indicating that C11ORF70 is involved in cytoplasmic assembly of dynein arms. Expression analyses of C11ORF70 showed that C11ORF70 is expressed in ciliated respiratory cells and that the expression of C11ORF70 is upregulated during ciliogenesis, similar to other previously described cytoplasmic dynein arm assembly factors. Furthermore, C11ORF70 shows an interaction with cytoplasmic ODA/IDA assembly factor DNAAF2, supporting our hypothesis that C11ORF70 is a novel preassembly factor involved in the pathogenesis of PCD. The identification of a novel genetic defect that causes PCD and male infertility is of great clinical importance as well as for genetic counselling.

scholarly journals Etiologies of abdominal pain emergencies in pediatrics

2021 ◽  
Author(s):  
Hala Atta Youssef ◽  
Aishah Mohammad Alkhaldi ◽  
Manar Mohammed Alshahrani ◽  
Abdullah Tariq Almalki ◽  
Amjad Ali Alahmari ◽  
...  
Keyword(s):  
Emergency Department ◽  
Abdominal Pain ◽  
Pediatric Patients ◽  
Surgical Intervention ◽  
Acute Abdominal Pain ◽  
Clinical Importance ◽  
Healthcare Settings ◽  
Common Causes ◽  
The Common ◽  
Attending Physicians

Reports showed that children usually complained of acute abdominal pain, which indicated the presence of severe underlying conditions and can have significant clinical importance. Serious challenges have been reported in healthcare settings where an urgent evaluation of the cases was necessary to adequately manage the patient before developing serious complications that might even end up with death. Some of these conditions included intussusception, appendicitis, volvulus and adhesions. Although estimates indicated that only around 1% of pediatric patients with acute abdominal pain usually required surgical intervention, concerns regarding the overlooking and misdiagnosis of significant conditions that might have severe prognostic outcomes were aroused among the different emergency departments. This study reviewed the common causes of acute abdominal pain among children admitted to the emergency department. Our results indicated that various etiologies can develop acute abdominal pain and therefore, establishing an adequate diagnosis by differentiating between the different etiologies should be done by the attending physicians to enhance the outcomes and adequately manage the admitted patients. Gastrointestinal causes of acute abdominal pain were the commonest to cause admissions to the emergency department. However, care should also be provided to the less common conditions, which might include genitourinary and pulmonary disorders and therefore, a thorough examination of children should be provided not to conduct a misdiagnosis of the underlying condition.

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