Neonatal Diabetes due to a Mutation in the Distal PTF1A Enhancer: A Case Report and Literature Review

: Biallelic variants in the pancreas-specific transcription factor 1A (PTF1A) gene are a rare cause of permanent neonatal diabetes. We report a case of neonatal diabetes with unique clinical manifestations. The clinical diagnosis of the affected infant was confirmed by insufficient endocrine and exocrine pancreas activity; however, the pancreas was normal in imaging. Molecular analyses identified a novel homozygous single nucleotide variant (Chr10, g.23508441T > G), affecting a highly conserved nucleotide within a distal enhancer of the PTF1A gene. The literature review showed that most of these patients had IUGR and imaging evidence of pancreatic agenesis or hypoplasia. We suggest that pancreatic imaging and evaluation of exocrine pancreas function can help early confirmation of the diagnosis in patients with permanent neonatal diabetes.

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Permanent Neonatal Diabetes Mellitus and Pancreatic Exocrine Insufficiency Resulting From Congenital Pancreatic Agenesis

Archives of Pediatrics and Adolescent Medicine ◽

10.1001/archpedi.1993.02160300013005 ◽

1993 ◽

Vol 147 (6) ◽

pp. 607 ◽

Cited By ~ 4

Author(s):

DANIEL L. METZGER

Keyword(s):

Diabetes Mellitus ◽

Neonatal Diabetes ◽

Neonatal Diabetes Mellitus ◽

Pancreatic Exocrine Insufficiency ◽

Exocrine Insufficiency ◽

Permanent Neonatal Diabetes ◽

Permanent Neonatal Diabetes Mellitus ◽

Pancreatic Agenesis ◽

Pancreatic Exocrine

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Neonatal Diabetes Mellitus in the Structure of IPEX Syndrome

Pediatrician (St Petersburg) ◽

10.17816/ped8299-104 ◽

2017 ◽

Vol 8 (2) ◽

pp. 99-104

Author(s):

Mariia E Turkunova ◽

Liliya V Ditkovskaya ◽

Evgenii N Suspitsin ◽

Ludmila V Tyrtova ◽

Ludmila A Jelenina ◽

...

Keyword(s):

Diabetes Mellitus ◽

Clinical Manifestations ◽

Neonatal Diabetes ◽

Skin Lesions ◽

Neonatal Diabetes Mellitus ◽

First Year ◽

Permanent Neonatal Diabetes ◽

Severity Of The Disease ◽

Clinical Triad ◽

First Year Of Life

This disease is characterized by the onset of primary immunodeficiency, which expresses itself as autoimmune multisystem failure, often clinically manifests during the first year of life; there are only about 150 cases in the world described by now. IPEX syndrome is caused by FOXP3 gene defect, which is a transcription factor that affects the activity of regulatory T-cells responsible for the maintenance of aytotolerance. There are around 70 pathogenic mutations in this gene described so far. Most patients with IPEX-syndrome have a clinical manifestations of the disease in the early neonatal period or during the first 3-4 months of life. For this disease the following clinical triad of manifestations is typical: Autoimmune enteropathy (100%), diabetes mellitus (70%), skin lesions (65%), as in the syndrome structure includes severe developmental delay (50%), thyroid disease (30%), recurrent infections (20%), rarer autoimmune cytopenia (Coombs-positive hemolytic anemia), pneumonia, nephritis, hepatitis, artrit, myositis, alopecia. However, some cases of later manifestations were described (in patients of more than 1 year of age) when patients did not show all clinical and laboratory symptoms typical for severe forms of the disease. Due to the severity of the disease and the high mortality in this group of patients, it is very important to diagnose it early and start therapy timely. The article describes a clinical case of permanent neonatal diabetes mellitus in the structure of IPEX syndrome.

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392 UNUSUAL CASE OF PERMANENT NEONATAL DIABETES IN A NEWBORN ATTRIBUTABLE TO PANCREATIC AGENESIS

Journal of Investigative Medicine ◽

10.2310/6650.2005.00006.391 ◽

2005 ◽

Vol 53 (1) ◽

pp. S323.2-S323

Author(s):

A. P. Ashraf ◽

H. Abdullatif ◽

J. M. Moates

Keyword(s):

Unusual Case ◽

Neonatal Diabetes ◽

Permanent Neonatal Diabetes ◽

Pancreatic Agenesis

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Amyand’s hernia in a child with permanent neonatal diabetes due to pancreatic agenesis.

Pediatric Reports ◽

10.4081/pr.2009.e6 ◽

2009 ◽

Vol 1 (1) ◽

Cited By ~ 2

Author(s):

Alessandro Giannattasio ◽

Riccardo Campus ◽

Monica Muraca ◽

Giorgio Lucigrai ◽

Renata Lorini ◽

...

Keyword(s):

Neonatal Diabetes ◽

Amyand’S Hernia ◽

Permanent Neonatal Diabetes ◽

Pancreatic Agenesis

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Influence of the Acetylation Type on the Incidence of Isoniazid-Induced Hepatotoxicity in Patients with Newly Diagnosed Pulmonary Tuberculosis

Antibiotics and Chemotherapy ◽

10.37489/0235-2990-2020-65-7-8-31-36 ◽

2020 ◽

Vol 65 (7-8) ◽

pp. 31-36

Author(s):

N. M. Krasnova ◽

N. E. Evdokimova ◽

A. A. Egorova ◽

O. I. Filippova ◽

E. A. Alekseeva ◽

...

Keyword(s):

Pulmonary Tuberculosis ◽

Clinical Laboratory ◽

Clinical Manifestations ◽

Normal Activity ◽

Slow Acetylators ◽

Nucleotide Polymorphisms ◽

Newly Diagnosed ◽

Single Nucleotide ◽

Tuberculosis Chemotherapy ◽

Genetically Determined

Introduction. Liver damage can be a dangerous side effect of using isoniazid. Individual susceptibility to isoniazid in humans is dependent on the presence of N-acetyltransferase 2 allelic variants in genome. It was imperative to assess the effect of genetically determined isoniazid acetylation rate in terms of risk of developing isoniazid-induced hepatotoxicity, as well as prevention of potential hepatopathy, and improvement of tuberculosis chemotherapy safety. Aim. To study the effect of acetylation type on the incidence of isoniazid hepatotoxicity in residents of the Sakha Republic (Yakutia) with newly diagnosed pulmonary tuberculosis. Methods. The study included 112 patients with newly diagnosed pulmonary tuberculosis. Genotyping was performed using real-time polymerase chain reaction. The following single nucleotide polymorphisms were studied: rs1801280, rs1799930, rs1799931, rs1799929, rs1208, rs1041983. Hepatotoxicity was determined based on the results of clinical laboratory monitoring and using the criteria developed by the European Association for the Study of the Liver (2019). Results. Hepatotoxic reactions developed more often in slow acetylators (43.2%), compared to fast acetylators (20.7%) and intermediate acetylators (10.9%); p=0.002. Serum alanine aminotransferase activity was 5 or more times above the upper limit of normal activity in 37.8% of slow acetylators, and in 8.7% of intermediate acetylators; p=0.001. Clinical manifestations of isoniazid hepatotoxicity were observed more often in slow acetylators (29.7%), than in fast acetylators (3.4%); p=0.000. Conclusion. Slow acetylation type ought to be considered an important risk factor for developing isoniazid hepatotoxicity in patients with pulmonary tuberculosis.

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Monogenic Diabetes: Genetics and Relevance on Diabetes Mellitus Personalized Medicine

Current Diabetes Reviews ◽

10.2174/1573399816666191230114352 ◽

2020 ◽

Vol 16 (8) ◽

pp. 807-819 ◽

Cited By ~ 1

Author(s):

Madalena Sousa ◽

Jácome Bruges-Armas

Keyword(s):

Diabetes Mellitus ◽

Complex Disease ◽

Clinical Manifestations ◽

Neonatal Diabetes ◽

Monogenic Diabetes ◽

Diabetes Genetics ◽

Individualize Treatment

Background: Diabetes mellitus (DM) is a complex disease with significant impression in today's world. Aside from the most common types recognized over the years, such as type 1 diabetes (T1DM) and type 2 diabetes (T2DM), recent studies have emphasized the crucial role of genetics in DM, allowing the distinction of monogenic diabetes. Methods: Authors did a literature search with the purpose of highlighting and clarifying the subtypes of monogenic diabetes, as well as the accredited genetic entities responsible for such phenotypes. Results: The following subtypes were included in this literature review: maturity-onset diabetes of the young (MODY), neonatal diabetes mellitus (NDM) and maternally inherited diabetes and deafness (MIDD). So far, 14 subtypes of MODY have been identified, while three subtypes have been identified in NDM - transient, permanent, and syndromic. Discussion: Despite being estimated to affect approximately 2% of all the T2DM patients in Europe, the exact prevalence of MODY is still unknown, accentuating the need for research focused on biomarkers. Consequently, due to its impact in the course of treatment, follow-up of associated complications, and genetic implications for siblings and offspring of affected individuals, it is imperative to diagnose the monogenic forms of DM accurately. Conclusion: Currently, advances in the genetics field allowed the recognition of new DM subtypes, which until now, were considered slight variations of the typical forms. Thus, it is imperative to act in the close interaction between genetics and clinical manifestations, to facilitate diagnosis and individualize treatment.

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Investigating Diseases and Chemicals in COVID-19 Literature with Text Mining (Preprint)

10.2196/preprints.21503 ◽

2020 ◽

Author(s):

Amir Karami ◽

Brandon Bookstaver ◽

Melissa Nolan

Keyword(s):

Text Mining ◽

Literature Review ◽

Topic Modeling ◽

Large Scale ◽

Clinical Manifestations ◽

International Health ◽

Research Papers ◽

Strategic Plans ◽

Funding Agencies ◽

The Relationship

BACKGROUND The COVID-19 pandemic has impacted nearly all aspects of life and has posed significant threats to international health and the economy. Given the rapidly unfolding nature of the current pandemic, there is an urgent need to streamline literature synthesis of the growing scientific research to elucidate targeted solutions. While traditional systematic literature review studies provide valuable insights, these studies have restrictions, including analyzing a limited number of papers, having various biases, being time-consuming and labor-intensive, focusing on a few topics, incapable of trend analysis, and lack of data-driven tools. OBJECTIVE This study fills the mentioned restrictions in the literature and practice by analyzing two biomedical concepts, clinical manifestations of disease and therapeutic chemical compounds, with text mining methods in a corpus containing COVID-19 research papers and find associations between the two biomedical concepts. METHODS This research has collected papers representing COVID-19 pre-prints and peer-reviewed research published in 2020. We used frequency analysis to find highly frequent manifestations and therapeutic chemicals, representing the importance of the two biomedical concepts. This study also applied topic modeling to find the relationship between the two biomedical concepts. RESULTS We analyzed 9,298 research papers published through May 5, 2020 and found 3,645 disease-related and 2,434 chemical-related articles. The most frequent clinical manifestations of disease terminology included COVID-19, SARS, cancer, pneumonia, fever, and cough. The most frequent chemical-related terminology included Lopinavir, Ritonavir, Oxygen, Chloroquine, Remdesivir, and water. Topic modeling provided 25 categories showing relationships between our two overarching categories. These categories represent statistically significant associations between multiple aspects of each category, some connections of which were novel and not previously identified by the scientific community. CONCLUSIONS Appreciation of this context is vital due to the lack of a systematic large-scale literature review survey and the importance of fast literature review during the current COVID-19 pandemic for developing treatments. This study is beneficial to researchers for obtaining a macro-level picture of literature, to educators for knowing the scope of literature, to journals for exploring most discussed disease symptoms and pharmaceutical targets, and to policymakers and funding agencies for creating scientific strategic plans regarding COVID-19.

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Genetic polymorphism for IFNγ +874T/A in patients with acute toxoplasmosis

Revista da Sociedade Brasileira de Medicina Tropical ◽

10.1590/s0037-86822012000600020 ◽

2012 ◽

Vol 45 (6) ◽

pp. 757-760 ◽

Cited By ~ 11

Author(s):

Elizabeth de Souza Neves ◽

André Luis Land Curi ◽

Maira Cavalcanti de Albuquerque ◽

Cassius Schnel Palhano-Silva ◽

Laura Berriel da Silva ◽

...

Keyword(s):

Single Nucleotide Polymorphism ◽

Case Control Study ◽

Severe Disease ◽

Clinical Manifestations ◽

Nucleotide Polymorphism ◽

Gene Encoding ◽

Single Nucleotide ◽

Duration Of Disease ◽

Acute Toxoplasmosis ◽

Control Study

INTRODUCTION: A single nucleotide polymorphism (SNP) in the gene encoding gamma interferon influences its production and is associated with severity of infectious diseases. This study aimed to evaluate the association of IFNγ+874T/A SNP with duration of disease, morbidity, and development of retinochoroiditis in acute toxoplasmosis. METHODS: A case-control study was conducted among 30 patients and 90 controls. RESULTS: Although statistical associations were not confirmed, A-allele was more common among retinochoroiditis cases and prolonged illness, while T-allele was more frequent in severe disease. CONCLUSIONS: Despite few cases, the results could indicate a relation between IFNγ+874T/A single nucleotide polymorphism and clinical manifestations of toxoplasmosis.

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