Neurometabolic Disorders Associated With Disturbances of Small Molecule Metabolism

2021 ◽  
pp. 1092-1105
Author(s):  
Deborah L. Renaud
Keyword(s):  
Small Molecule ◽  
Inborn Errors Of Metabolism ◽  
Clinical Symptoms ◽  
Inborn Errors ◽  
Biochemical Processes ◽  
Live Births ◽  
Biochemical Pathways ◽  
Neurometabolic Disorders ◽  
Acute Exacerbations

Inborn errors of metabolism affect approximately 1 in 1,000 to 1 in 3,000 live births. Most of these inherited conditions are autosomal recessive, although a few are autosomal dominant or X-linked. Mitochondrial DNA disorders may be maternally inherited. The clinical symptoms associated with inborn errors of metabolism reflect the disruption of normal biochemical processes required for synthesis, breakdown, or transport of metabolites. This impairment leads to accumulation of metabolites that cause toxic effects, inadequate levels of metabolites required for normal cellular activity, or secondary disruption of essential metabolic pathways. Small molecule disorders involve the metabolism of amino acids, organic acids, carbohydrates, fatty acids, and other biochemical pathways. These disorders may present with acute exacerbations superimposed on long-term neurologic symptoms.

scholarly journals Inborn Errors of Metabolism Collaborative: large-scale collection of data on long-term follow-up for newborn-screened conditions

2016 ◽  
Vol 18 (12) ◽  
pp. 1276-1281 ◽  
Author(s):  
Susan A. Berry ◽  
◽  
Nancy D. Leslie ◽  
Mathew J. Edick ◽  
Sally Hiner ◽  
...  
Keyword(s):  
Inborn Errors Of Metabolism ◽  
Large Scale ◽  
Inborn Errors ◽  
Long Term Follow Up

Disorders of Creatine Metabolism

2016 ◽  
Author(s):  
David Cheillan ◽  
Frédéric Sedel
Keyword(s):  
Language Impairment ◽  
Body Fluid ◽  
Inborn Errors Of Metabolism ◽  
Clinical Symptoms ◽  
Creatine Supplementation ◽  
Speech Delay ◽  
Inborn Errors ◽  
Creatine Transporter ◽  
Creatine Metabolism ◽  
Early Diagnostic

Creatine is a physiological guanidino compound playing a major role in energy metabolism in muscle and implicated in neurotransmission in brain. The three disorders of creatine metabolism (AGAT and GAMT deficiencies and the X-linked creatine transporter defect) are a group of inborn errors of metabolism characterized by a depletion of creatine that could be easily diagnosed by mesasurement of guanidinoacetate and creatine in body fluid or cranial MRS spectroscopy. The main clinical features of these paediatric disorders are intellectual disability and speech delay and some adult patients have been described with severe language impairment and mental retardation. Although the X-linked creatine transporter defect is currently not treatable, the clinical symptoms of the two disorders of creatine synthesis should be improved by creatine supplementation emphasizing the importance of an early diagnostic.

scholarly journals Precision of a Clinical Metabolomics Profiling Platform for Use in the Identification of Inborn Errors of Metabolism

2020 ◽  
Vol 5 (2) ◽  
pp. 342-356 ◽  
Author(s):  
Lisa Ford ◽  
Adam D Kennedy ◽  
Kelli D Goodman ◽  
Kirk L Pappan ◽  
Anne M Evans ◽  
...  
Keyword(s):  
Inborn Errors Of Metabolism ◽  
Metabolic Diseases ◽  
Clinical Laboratory ◽  
Inborn Errors ◽  
Biochemical Pathways ◽  
Whole Exome ◽  
Multiple Biomarkers ◽  
Sample Testing ◽  
Precision Study ◽  
Clinical Metabolomics

Abstract Background The application of whole-exome sequencing for the diagnosis of genetic disease has paved the way for systems-based approaches in the clinical laboratory. Here, we describe a clinical metabolomics method for the screening of metabolic diseases through the analysis of a multi-pronged mass spectrometry platform. By simultaneously measuring hundreds of metabolites in a single sample, clinical metabolomics offers a comprehensive approach to identify metabolic perturbations across multiple biochemical pathways. Methods We conducted a single- and multi-day precision study on hundreds of metabolites in human plasma on 4, multi-arm, high-throughput metabolomics platforms. Results The average laboratory coefficient of variation (CV) on the 4 platforms was between 9.3 and 11.5% (median, 6.5–8.4%), average inter-assay CV on the 4 platforms ranged from 9.9 to 12.6% (median, 7.0–8.3%) and average intra-assay CV on the 4 platforms ranged from 5.7 to 6.9% (median, 3.5–4.4%). In relation to patient sample testing, the precision of multiple biomarkers associated with IEM disorders showed CVs that ranged from 0.2 to 11.0% across 4 analytical batches. Conclusions This evaluation describes single and multi-day precision across 4 identical metabolomics platforms, comprised each of 4 independent method arms, and reproducibility of the method for the measurement of key IEM metabolites in patient samples across multiple analytical batches, providing evidence that the method is robust and reproducible for the screening of patients with inborn errors of metabolism.

Evaluation and long-term follow-up of infants with inborn errors of metabolism identified in an expanded screening programme

2011 ◽  
Vol 104 (4) ◽  
pp. 470-475 ◽  
Author(s):  
Ma Luz Couce ◽  
Daisy E. Castiñeiras ◽  
Ma Dolores Bóveda ◽  
Ana Baña ◽  
José A. Cocho ◽  
...  
Keyword(s):  
Inborn Errors Of Metabolism ◽  
Screening Programme ◽  
Inborn Errors ◽  
Long Term Follow Up

scholarly journals METABOLIC EMERGENCIES – PART I

2015 ◽  
Vol 64 (1) ◽  
pp. 5-9
Author(s):  
Dana-Teodora Anton-Paduraru ◽  
Keyword(s):  
Metabolic Acidosis ◽  
Inborn Errors Of Metabolism ◽  
Metabolic Diseases ◽  
Clinical Symptoms ◽  
Inborn Errors ◽  
Recommended Treatment ◽  
Metabolic Conditions ◽  
Neonatal Hypocalcemia

Often, patients with metabolic conditions (diseases caused by electrolytic unbalances, endocrine dysfunctions, inborn errors of metabolism) have symptoms similar to other emergencies, particularly as newborns and infants. The authors present the main emergencies: electrolytic unbalances – hypoglycemia, hyponatremia, metabolic acidosis and neonatal hypocalcemia; endocrine dysfunctions – suprarenal insufficiency and neonatal hypopituitarism; inborn metabolic diseases – acidosis, hyperglycemia/ hypoglycemia, hyperammoniemia, clinical symptoms associated to them, and recommended treatment.

Inborn errors of metabolism in a neonatology unit: Impact and long-term results

2011 ◽  
Vol 53 (1) ◽  
pp. 13-17 ◽  
Author(s):  
Ma Luz Couce ◽  
Ana Baña ◽  
Ma Dolores Bóveda ◽  
Alejandro Pérez-Muñuzuri ◽  
José Ramón Fernández-Lorenzo ◽  
...  
Keyword(s):  
Inborn Errors Of Metabolism ◽  
Long Term Results ◽  
Inborn Errors

scholarly journals TURNING THE OXYGEN DIAL AS A THERAPY: HYPOXIA TREATMENT FOR MITOCHONDRIAL DYSFUNCTION

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S395-S395
Author(s):  
Isha Jain
Keyword(s):  
Mitochondrial Dysfunction ◽  
Inborn Errors Of Metabolism ◽  
Chronic Hypoxia ◽  
Phase 1 ◽  
Disease Model ◽  
Inborn Errors ◽  
Phase 1 Clinical Trial ◽  
Live Births ◽  
Hypoxia Treatment ◽  
Novel Therapeutic

Abstract Mitochondrial disease affects 1 in 4800 live births, with little in the way of therapies. We found that chronic hypoxia extends the life of a Complex 1 disease model by 5-fold. Starting hypoxia therapy at a late-stage of disease can even reverse the MRI-detectable lesions. At the other extreme, mild hyperoxia greatly exacerbates disease and leads to death within several days. These findings have now led to a phase 1 clinical trial in healthy volunteers, with the ultimate goal of human translation. We believe we have identified a new mode of treatment that will be broadly applicable to different forms of mitochondrial dysfunction, ranging from rare inborn errors of metabolism to more common, age-associated pathologies. We believe that “turning the oxygen dial” to low or high oxygen will serve as a novel therapeutic for a range of conditions in the coming years.

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.

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