scholarly journals Syndromic Inherited Retinal Diseases: Genetic, Clinical and Diagnostic Aspects

Diagnostics ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 779
Author(s):  
Yasmin Tatour ◽  
Tamar Ben-Yosef
Keyword(s):  
Inborn Errors Of Metabolism ◽  
Phenotypic Variability ◽  
Genetic Diseases ◽  
Correct Diagnosis ◽  
Clinical Findings ◽  
Retinal Diseases ◽  
Inborn Errors ◽  
Diagnostic Aspects ◽  
The Central Nervous System ◽  
High Degree

Inherited retinal diseases (IRDs), which are among the most common genetic diseases in humans, define a clinically and genetically heterogeneous group of disorders. Over 80 forms of syndromic IRDs have been described. Approximately 200 genes are associated with these syndromes. The majority of syndromic IRDs are recessively inherited and rare. Many, although not all, syndromic IRDs can be classified into one of two major disease groups: inborn errors of metabolism and ciliopathies. Besides the retina, the systems and organs most commonly involved in syndromic IRDs are the central nervous system, ophthalmic extra-retinal tissues, ear, skeleton, kidney and the cardiovascular system. Due to the high degree of phenotypic variability and phenotypic overlap found in syndromic IRDs, correct diagnosis based on phenotypic features alone may be challenging and sometimes misleading. Therefore, genetic testing has become the benchmark for the diagnosis and management of patients with these conditions, as it complements the clinical findings and facilitates an accurate clinical diagnosis and treatment.

A case of fixation amnesia in Langerhans cell histiocytosis involving the central nervous system

2020 ◽  
Vol 12 (6) ◽  
pp. 117-123
Author(s):  
L. V. Lukina ◽  
V. A. Mikhailov ◽  
N. I. Ananyeva ◽  
G. E. Mazo ◽  
L. I. Sitnik ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Langerhans Cell Histiocytosis ◽  
Correct Diagnosis ◽  
Brain Lesion ◽  
Clinical Findings ◽  
Langerhans Cell ◽  
Unknown Etiology ◽  
Bone Lesions ◽  
The Central Nervous System

Langerhans cell histiocytosis (LCH) is a rare disease with hitherto unknown etiology and pathogenesis. It is extremely rare for clinicians to encounter histiocytic lesions of the central nervous system (CNS); the proportion of cases of which is only 1–4% of all polysystemic and multifocal bone lesions. The paper describes a clinical case of fixation amnesia in a female patient with focal brain lesions in LCH. It depicts the most characteristic clinical features and presents an algorithm for the diagnosis of histiocytic brain lesion. The results of the experimental psychological examination of the patient are considered in detail and the clinical presentations of fixation amnesia are described. There are neuroimaging data showing the lesions in the hypothalamic-pituitary region and temporal bone, which involve the auditory structures. The clinical findings have led to the conclusion that both the clinical and neuroimaging patterns of histiocytic lesions in the CNS are non-specific, which complicates the diagnostic search in LCH. For correct diagnosis and timely treatment, it is necessary to perform a biopsy of the pathological focus, followed by histological and immunohistochemical examination of the material.

scholarly journals Inborn Errors of Metabolism-Clinical Findings and Laboratory Tests at the Children’s Medical Center, Tehran, Iran

2016 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Farzaneh Abbasi ◽  
Aria Setoodeh ◽  
Fatemeh Sayarifard ◽  
Parastoo Rostami ◽  
Ali Rabbani
Keyword(s):  
Laboratory Tests ◽  
Inborn Errors Of Metabolism ◽  
Medical Center ◽  
Clinical Findings ◽  
Inborn Errors

The inborn errors of metabolism: General aspects

2020 ◽  
pp. 1929-1941
Author(s):  
Timothy M. Cox ◽  
Richard W.E. Watts
Keyword(s):  
Inborn Errors Of Metabolism ◽  
Quaternary Structure ◽  
Correct Diagnosis ◽  
Gene Replacement ◽  
Inborn Errors ◽  
Irreversible Damage ◽  
Presymptomatic Stage ◽  
General Aspects ◽  
High Level

The inborn errors of metabolism are those inherited diseases in which the phenotype includes a characteristic constellation of biochemical abnormalities related to an alteration in the catalytic activity of a single specific enzyme, activator, or transport protein. Mechanism of diseases—mutations in the proteins giving rise to the inborn errors of metabolism affect primary, secondary, tertiary, or quaternary structure. This can lead to an enormous variety of consequences. Clinical presentation—the manifestations of metabolic disease are protean and may seem nondescript, especially in adults, hence a high level of suspicion may be required to make a correct diagnosis. Prevention and screening—there is a strong case for mass population screening for some inborn errors of metabolism at the presymptomatic stage to allow early detection and introduction of proven treatment before irreversible damage occurs. Management—definitive cure of the underlying abnormality is available for a few disorders, but precise characterization of the biochemical disturbance often permits rational treatment to be organized and provides the basis for further therapeutic endeavours. General approaches include (1) restriction of a substrate that cannot be metabolized including molecules derived from the diet; (2) replacement of a missing metabolic product; (3) removal of poisonous metabolites or rebalancing overproduction of toxic intermediates; (4) administering pharmacological doses of a cofactor, sometimes a vitamin, that may also stabilize a mutant enzyme; (5) replacement of a missing gene product, usually by enzymatic augmentation therapy or pharmacological chaperones, to prevent premature aggregation and denaturation; (6) repression of an overproduced protein or metabolite by stable RNA inhibition; (7) transplantation of cells or organs as a ‘gene replacement therapy’; and (8) activation of a poorly functioning protein.

scholarly journals Untargeted Metabolomics-Based Screening Method for Inborn Errors of Metabolism using Semi-Automatic Sample Preparation with an UHPLC- Orbitrap-MS Platform

Metabolites ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 289 ◽  
Author(s):  
Ramon Bonte ◽  
Michiel Bongaerts ◽  
Serwet Demirdas ◽  
Janneke G. Langendonk ◽  
Hidde H. Huidekoper ◽  
...  
Keyword(s):  
Sample Preparation ◽  
Inborn Errors Of Metabolism ◽  
Correct Diagnosis ◽  
Screening Method ◽  
Current Approach ◽  
Untargeted Metabolomics ◽  
Metabolic Phenotype ◽  
Inborn Errors ◽  
New Biomarkers ◽  
Orbitrap Ms

Routine diagnostic screening of inborn errors of metabolism (IEM) is currently performed by different targeted analyses of known biomarkers. This approach is time-consuming, targets a limited number of biomarkers and will not identify new biomarkers. Untargeted metabolomics generates a global metabolic phenotype and has the potential to overcome these issues. We describe a novel, single platform, untargeted metabolomics method for screening IEM, combining semi-automatic sample preparation with pentafluorophenylpropyl phase (PFPP)-based UHPLC- Orbitrap-MS. We evaluated analytical performance and diagnostic capability of the method by analysing plasma samples of 260 controls and 53 patients with 33 distinct IEM. Analytical reproducibility was excellent, with peak area variation coefficients below 20% for the majority of the metabolites. We illustrate that PFPP-based chromatography enhances identification of isomeric compounds. Ranked z-score plots of metabolites annotated in IEM samples were reviewed by two laboratory specialists experienced in biochemical genetics, resulting in the correct diagnosis in 90% of cases. Thus, our untargeted metabolomics platform is robust and differentiates metabolite patterns of different IEMs from those of controls. We envision that the current approach to diagnose IEM, using numerous tests, will eventually be replaced by untargeted metabolomics methods, which also have the potential to discover novel biomarkers and assist in interpretation of genetic data.

scholarly journals Course for the qualification of nurses in the care of children with genetic diseases: an experience report

2021 ◽  
Vol 42 (spe) ◽  
Author(s):  
Silvani Herber ◽  
Fernanda Araújo Rodrigues ◽  
Alessandra Vaccari
Keyword(s):  
Professional Development ◽  
Inborn Errors Of Metabolism ◽  
Screening Program ◽  
Genetic Diseases ◽  
Public University ◽  
Experience Report ◽  
Southern Brazil ◽  
Team Leaders ◽  
Inborn Errors ◽  
Face To Face

ABSTRACT Objective To describe the experience of developing and operating an extension course to qualify nurses in the care of children with genetic diseases. Method An experience report about the conduction of a university extension course with eight participants, developed at a public university in southern Brazil. It was a face-to-face course in November 2019. Results The course covered the following themes: introduction to Genetics in Nursing; rare diseases; inborn errors of metabolism; Neonatal Screening Program; and microcephaly. The content was developed through theoretical aspects, presentation of clinical cases, practical activities, and realistic simulation. Conclusion The extension course provided knowledge to nurses, who develop their functions as team leaders, enabling professional development and the promotion of information on the topic, which corroborates the objectives of the Nursing Now campaign.

scholarly journals Citrullinemia and Hyperglycinemia Presenting with Seizures - Case Report of a 4 Day Old Baby

2013 ◽  
Vol 3 (1) ◽  
pp. 17-20
Author(s):  
Moushumi Lodh ◽  
Joshi Anand Kerketta
Keyword(s):  
Case Report ◽  
Amino Acid ◽  
Inborn Error ◽  
Inborn Errors Of Metabolism ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Review Of The Literature ◽  
Medical Sciences ◽  
Inborn Errors ◽  
High Degree

Inborn errors of amino acid metabolism (IEM) are of concern in India, the spectrum being wide, varied and poorly diagnosed. Since aggregate incidence of inborn errors of metabolism is relatively high, in countries such as India, a high degree of suspicion is essential to correctly diagnose an inborn error of amino acid metabolism. We report a case of citrullinemia, glycinemia with hyperammonaemia and seizures in a 4-dayold previously asymptomatic baby, with a brief review of the literature. DOI: http://dx.doi.org/10.3126/ajms.v3i1.4801 Asian Journal of Medical Sciences 3(2012) 17-20

scholarly journals The digital epidemiology of phenylketonuria, aka folling’s disease: retrospective analysis and geographic mapping via google trends

2018 ◽  
Vol 9 (6) ◽  
pp. 93-99
Author(s):  
Ahmed Al-Imam
Keyword(s):  
Inborn Errors Of Metabolism ◽  
Predictive Analytics ◽  
Middle Eastern ◽  
Genetic Diseases ◽  
Google Trends ◽  
Inborn Errors ◽  
Geographic Mapping ◽  
Multiple Organs ◽  
Digital Epidemiology ◽  
Surface Web

Background: Phenylketonuria, commonly known as PKU, is an inherited disorder in which there is an abnormally elevated blood level of the amino acid phenylalanine leading to several pathologies affecting multiple organs including the central nervous system and resulting in debilitating intellectual disability and other neuropsychiatric disorders. Phenylalanine is a building block of several critical proteins within the biological systems.Aims and Objective: To assess the digital epidemiology and geographic mapping of Phenylketonuria.Materials and Methods: This study is a retrospective analytic (2013‑2017) of a very large database existing on the surface web known as Google Trends. it aims to extrapolate a statistical inference concerning the digital epidemiology and the geographic mapping of phenylketonuria. The trends database will be explored via thematic keywords specific to the condition of phenylketonuria including “Phenylketonuria [PKU]”, “Phenylalanine”, “Inborn errors of metabolism”, “Tetrahydrobiopterin”, and “Chromosome 12 (human)”.Results: The digital epidemiology is densely clustered in countries from the developed world, eastern Europe, and Latin America. Surface web users from China appears to possess the highest interest in phenylketonuria. The contribution of the Middle Eastern and Arabic countries to the geographic mapping did not exceed 10.51% at its best. Significant changes existed for year-to-year variations of trends. Statistical outliers were also found, the strongest of which was observed during April 2016 for which there’s no plausible explanation.Conclusion: Trends databases operating on the surface web represent potent tools of big data that can be exploited to assess the digital epidemiology and geographic mapping of countless phenomenon including rare genetic diseases and inborn errors of metabolism. There are also enormous potentials for real-time and predictive analytics of these databases when investing the application of automation in data collection and principles of machine learning.Asian Journal of Medical Sciences Vol.9(6) 2018 93-99

scholarly journals Development and application targeted NGS panels in the selective screening algorithm for inborn errors of metabolism. An experience of the St. Petersburg Medical and Genetic Center

2020 ◽  
pp. 66-68
Author(s):  
Ю.А. Чурюмова ◽  
Н.В. Вохмянина ◽  
С.В. Шляга ◽  
Т.В. Вавилова ◽  
Т.С. Симакова ◽  
...  
Keyword(s):  
Inborn Errors Of Metabolism ◽  
Clinical Symptoms ◽  
Genetic Diseases ◽  
Selective Screening ◽  
Inborn Errors ◽  
Leading Role ◽  
Childhood Morbidity ◽  
Screening Algorithm ◽  
Targeted Ngs ◽  
Biochemical Testing

Наследственные болезни обмена веществ представляют собой обширный класс генетических заболеваний и вносят значительный вклад в детскую заболеваемость, при этом их диагностика с использованием биохимических методов зачастую вызывает затруднения. В СПбГКУЗ МГЦ были разработаны и внедрены три панели для секвенирования 88 генов, ответственных за развитие трех групп наследственных болезней обмена (НБО), и протестировано 84 ребенка, у которых данные заболевания были заподозрены по данным тандемной масс-спектрометрии (ТМС), либо по наличию клинических симптомов. У 6 детей методом NGS полностью установлена генетическая причина заболевания. Патогенные мутации выявлялись значительно чаще при повышении биохимических маркеров, демонстрируя ведущую роль предварительного биохимического скрининга в проведении NGS анализа. NGS значительно повышает результативность клинической диагностики НБО. Биохимическое тестирование и NGS играют взаимодополняющие роли, и их комплексное использование в алгоритме селективного скрининга позволяет повысить точность диагностики НБО. Inborn errors of metabolism are an extensive class of genetic diseases and contribute significantly to childhood morbidity, and their diagnosis using biochemical methods is often difficult. Three panels for sequencing of 88 genes responsible for the development of three groups of inborn errors of metabolism (IEM) were developed and introduced in St.Petersburg Medical and Genetic Center and 84 children were tested for which these diseases were suspected by tandem mass-spectrometry or by the presence of clinical symptoms. In 6 children, the NGS method fully established the genetic cause of the disease. Pathogenic mutations were detected significantly more frequently with increased biochemical markers, demonstrating the leading role of pre-biochemical screening in performing NGS analysis. NGS significantly improves the clinical diagnostic effectiveness of IEM. Biochemical testing and NGS play complementary roles and their complex use in selective screening algorithm allows to increase accuracy of IEM diagnostics.

Inborn Errors of Metabolism— A Challenge to the Clinical Chemist

1975 ◽  
Vol 21 (1) ◽  
pp. 63-66 ◽  
Author(s):  
Lorentz Eldjarn ◽  
Egil Jellum ◽  
O Stokke
Keyword(s):  
Inborn Errors Of Metabolism ◽  
Clinical Chemistry ◽  
Inborn Errors ◽  
Diagnostic Aspects

Abstract No country has as yet established satisfactory plans for combating inborn errors of metabolism. The problem is great and very complex. Some 150-200 inborn errors of metabolism are known at present, but it is likely that the types so far described only represent a fraction of those actually occurring. Until now the field of inborn errors has been dominated by pediatricians, geneticists, and biochemists. Based on his knowledge both in medicine and in biochemistry, the clinical chemist should also play an important role, and consider the diagnostic aspects of this field to be part of his responsibility. In addition, he should also take part in the further work that often is necessary to elucidate these "biochemical" disorders. The bridging of benchside and bedside medicine should be looked upon as one of the main tasks of clinical chemistry, and in the field of inborn errors such a bridging will be of great importance.

Sign in / Sign up

Export Citation Format

Share Document