scholarly journals L-Carnitine and Acylcarnitines: Mitochondrial Biomarkers for Precision Medicine

Metabolites ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 51
Author(s):  
Marc R. McCann ◽  
Mery Vet George De la Rosa ◽  
Gus R. Rosania ◽  
Kathleen A. Stringer
Keyword(s):  
Precision Medicine ◽  
Inborn Errors Of Metabolism ◽  
Clinical Utility ◽  
Biomarker Discovery ◽  
Genetic Disorders ◽  
Acid Oxidation ◽  
Inborn Errors ◽  
Therapeutic Decisions ◽  
Literature Evidence ◽  
Clinical Biomarker

Biomarker discovery and implementation are at the forefront of the precision medicine movement. Modern advances in the field of metabolomics afford the opportunity to readily identify new metabolite biomarkers across a wide array of disciplines. Many of the metabolites are derived from or directly reflective of mitochondrial metabolism. L-carnitine and acylcarnitines are established mitochondrial biomarkers used to screen neonates for a series of genetic disorders affecting fatty acid oxidation, known as the inborn errors of metabolism. However, L-carnitine and acylcarnitines are not routinely measured beyond this screening, despite the growing evidence that shows their clinical utility outside of these disorders. Measurements of the carnitine pool have been used to identify the disease and prognosticate mortality among disorders such as diabetes, sepsis, cancer, and heart failure, as well as identify subjects experiencing adverse drug reactions from various medications like valproic acid, clofazimine, zidovudine, cisplatin, propofol, and cyclosporine. The aim of this review is to collect and interpret the literature evidence supporting the clinical biomarker application of L-carnitine and acylcarnitines. Further study of these metabolites could ultimately provide mechanistic insights that guide therapeutic decisions and elucidate new pharmacologic targets.

scholarly journals The Ophthalmological Manifestations of Various Inborn Errors of Metabolism: A Narrative Review

2021 ◽  
Vol 9 (2) ◽  
pp. 137-144
Author(s):  
Abdolreza Medghalchi ◽  
◽  
Afagh Hassanzadeh Rad ◽  
Setila Dalili ◽  
◽  
...  
Keyword(s):  
Inborn Errors Of Metabolism ◽  
Genetic Disorders ◽  
Single Gene ◽  
Scientific Information ◽  
Narrative Review ◽  
Inborn Errors ◽  
Relevant Evidence ◽  
Ocular Manifestations ◽  
Inherited Metabolic Disorders

Context: Inborn errors of metabolism or Inherited Metabolic Disorders (IMD) are a class of genetic disorders that occur because of single-gene defects. Evidence Acquisition: In this narrative review article, the authors searched Institute for Scientific Information (ISI), Web of Science, PubMed, and Google Scholar for the relevant evidence. Results: The ocular manifestations of IMDs can be distinguished in different diseases such as Albinism, Cystinosis, Homocystinuria, and Sulfite oxidize deficiency, Mannosidosis, Fucosidosis, Sialidosis, etc. Conclusions: Due to the direct toxic mechanisms of abnormal metabolites on eyes and regarding the effect of eye monitoring on the follow-up, management, and treatment, a detailed ophthalmological assessment is essential.

Inborn errors of metabolism diagnosed in sudden death cases by acylcarnitine analysis of postmortem bile

1995 ◽  
Vol 41 (8) ◽  
pp. 1109-1114 ◽  
Author(s):  
M S Rashed ◽  
P T Ozand ◽  
M J Bennett ◽  
J J Barnard ◽  
D R Govindaraju ◽  
...  
Keyword(s):  
Inborn Errors Of Metabolism ◽  
Dehydrogenase Deficiency ◽  
Sudden Infant Death ◽  
Diagnostic Methods ◽  
First Episode ◽  
Acid Oxidation ◽  
Sudden Infant ◽  
Inborn Errors ◽  
Postmortem Diagnosis ◽  
Acylcarnitine Analysis

Abstract Fatty acid oxidation (FAO) disorders represent a frequently misdiagnosed group of inborn errors of metabolism. Some patients die at the first episode of fasting intolerance and, if appropriate investigations are not undertaken, often meet the criteria of sudden infant death syndrome (SIDS). To expand existing protocols for the postmortem diagnosis of FAO and other metabolic disorders, we tested the hypothesis that analysis for acylcarnitine in bile, a specimen readily available at autopsy, may be utilized for diagnostic purposes. Using electrospray/tandem mass spectrometry, we analyzed for acylcarnitine postmortem bile specimens from two infants with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency, one infant with glutaryl-CoA dehydrogenase deficiency, and 17 uninformative SIDS cases as controls. The affected cases, and none of the controls, showed marked accumulation of C10-C18 acylcarnitines or glutarylcarnitine (acyl/free carnitine ratio: 5.2, 2.7, and 1.9, respectively; controls 0.2 +/- 0.1). In one patient, all other diagnostic methods were uninformative, suggesting that bile acylcarnitine profiling could lead to identification of previously overlooked cases.

scholarly journals Biomarker Discovery, Disease Classification, and Similarity Query Processing on High-Throughput MS/MS Data of Inborn Errors of Metabolism

2005 ◽  
Vol 11 (1) ◽  
pp. 90-99 ◽  
Author(s):  
Christian Baumgartner ◽  
Daniela Baumgartner
Keyword(s):  
Inborn Errors Of Metabolism ◽  
Biomarker Discovery ◽  
Expert Knowledge ◽  
Propionic Acidemia ◽  
Disease Classification ◽  
Therapeutic Interventions ◽  
Data Sets ◽  
Type I ◽  
Inborn Errors ◽  
Discriminatory Performance

In newborn errors of metabolism, biomarkers are urgently needed for disease screening, diagnosis, and monitoring of therapeutic interventions. This article describes a 2-step approach to discovermetabolic markers, which involves (1) the identification ofmarker candidates and (2) the prioritization of thembased on expert knowledge of diseasemetabolism. For step 1, the authors developed a new algorithm, the biomarker identifier (BMI), to identifymarkers fromquantified diseased versus normal tandemmass spectrometry data sets. BMI produces a ranked list ofmarker candidates and discards irrelevant metabolites based on a quality measure, taking into account the discriminatory performance, discriminatory space, and variance ofmetabolites’ concentrations at the state of disease. To determine the ability of identified markers to classify subjects, the authors compared the discriminatory performance of several machine-learning paradigms and described a retrieval technique that searches and classifies abnormal metabolic profiles from a screening database. Seven inborn errors of metabolism— phenylketonuria (PKU), glutaric acidemia type I (GA-I), 3-methylcrotonylglycinemia deficiency (3-MCCD), methylmalonic acidemia (MMA), propionic acidemia (PA), medium-chain acylCoAdehydrogenase deficiency (MCADD), and 3-OH longchain acyl CoA dehydrogenase deficiency (LCHADD)—were investigated. All primarily prioritized marker candidates could be confirmed by literature. Somenovel secondary candidateswere identified (i.e., C16:1 andC4DCfor PKU, C4DCfor GA-I, and C18:1 forMCADD), which require further validation to confirmtheir biochemical role during health and disease.

scholarly journals The relationship between the characteristics of burst suppression pattern and different etiologies in epilepsy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Haipo Yang ◽  
Pan Gong ◽  
Xianru Jiao ◽  
Qiujun Zhou ◽  
Yuehua Zhang ◽  
...  
Keyword(s):  
Inborn Errors Of Metabolism ◽  
Genetic Disorders ◽  
Burst Suppression ◽  
Inborn Errors ◽  
Ohtahara Syndrome ◽  
Genetic Epilepsies ◽  
The Relationship ◽  
Electroencephalogram Eeg ◽  
Myoclonic Encephalopathy ◽  
Early Myoclonic Encephalopathy

AbstractTo analyze the relationship between the characteristics of burst suppression (BS) pattern and different etiologies in epilepsy. Patients with a BS pattern who were younger than 6 months old were screened from our electroencephalogram (EEG) database. The synchronized and symmetric BS patterns under different etiologies in epilepsy were analyzed. A total of 32 patients had a BS pattern on EEG. The etiologies included genetic disorders (37.5%), cortical malformations (28.1%), inborn errors of metabolism (12.5%), and unknown (21.9%). Twenty-five patients were diagnosed with Ohtahara syndrome, one as early myoclonic encephalopathy, and one as epilepsy of infancy with migrating focal seizure. Five cases could not be classified into any epileptic syndrome. Asynchronous BS pattern was identified in 18 cases, of which 13 (72%) patients had genetic and/or metabolic etiologies. Synchronous BS pattern was identified in 14 cases, of which 8 (57%) patients had structural etiologies. Twenty-three patients had symmetric BS patterns, of which 15 (65%) patients had genetic etiologies. Nine patients had asymmetric BS patterns, of which 8 (89%) patients had structural etiologies. Patients with genetic epilepsies tended to have asynchronous and symmetric BS patterns, whereas those with structural epilepsies were more likely to have synchronous and asymmetric BS patterns.

Metabolic Disorders

2016 ◽  
Author(s):  
Lance Rodan
Keyword(s):  
Inborn Errors Of Metabolism ◽  
Urea Cycle ◽  
Acid Oxidation ◽  
Catabolic Pathway ◽  
Peroxisomal Disorders ◽  
Inborn Errors ◽  
Lysosomal Disorders ◽  
Cycle Disorders ◽  
Cobalamin Disorders

Inborn errors of metabolism (IEM) are individually rare but have a collective incidence of approximately one in 1000. Most IEM can manifest with neurologic symptoms. It is crucial for the pediatric neurologist to be familiar with the evaluation and management of these disorders because many are amenable to specific treatments. This review provides a category-based approach to the diagnosis and treatment of IEM organized by metabolic pathway and organelle. Categories include disorders of mitochondrial fatty acid oxidation and carnitine metabolism, urea cycle disorders, organic acidemias, aminoacidopathies, lysosomal disorders, peroxisomal disorders, vitamin- and diet-responsive metabolic epilepsies, and neurotransmitter disorders. Multiple summary tables for quick reference are provided. Figures show mitochondrial β-oxidation and carnitine cycle; urea cycle; T2-weighted magnetic resonance images (MRI) of ornithine transcarbamylase deficiency presenting with hyperammonemic encephalopathy, propionic academia, methylmalonic academia, glutaric acidemia type 1, ethylmalonic encephalopathy, mitochondrial complex 1 deficiency, pyruvate dehydrogenase complex E3 deficiency, untreated biotin-thiamine-responsive basal ganglia disease, homocysteinemia and low plasma methionine (suspected remethylation defect), attenuated Krabbe disease, Hunter syndrome, and GM1-gangliosidosis; branched-chain amino acid catabolic pathway; lysine, hydroxylysine, and tryptophan catabolic pathway; intracellular cobalamin metabolism; metabolism of homocysteine; diffusion-weighted imaging of maple syrup urine disease, nonketotic hyperglycinemia, and poorly controlled phenylketonuria; sphingolipid metabolic pathway; skeletal surveys of Hurler syndrome demonstrating features of dysostosis multiplex and rhizomelic chondrodysplasia punctata type 1; MRI of Salla disease; peroxisomal oxidation reactions, and the biogenic amine biosynthetic pathway. Tables list fatty acid oxidation and carnitine disorders, metabolic myopathies presenting with recurrent rhabdomyolysis, urea cycle disorders, organic acidemias, IEM associated with abnormal head size, cobalamin disorders, aminoacidopathies, IEM associated with abnormal odor, lysosomal disorders, lysosomal disease Symptom categories (Not mutually exclusive), peroxisomal disorders, IEM associated with brain malformations, vitamin- and diet-responsive epilepsies, neurotransmitter disorders, and IEM associated with brain mineralization. This review contains 26 highly rendered figures, 15 tables, and 71 references. Key words: Inborn errors of metabolism, organic acidemia, cobalamin disorders, aminoacidopathy, lysosomal disorders

scholarly journals Complex patterns of inheritance, including synergistic heterozygosity, in inborn errors of metabolism: Implications for precision medicine driven diagnosis and treatment

2019 ◽  
Vol 128 (1-2) ◽  
pp. 1-9 ◽  
Author(s):  
Jerry Vockley ◽  
Steven F. Dobrowolski ◽  
Georgianne L. Arnold ◽  
Ruben Bonilla Guerrero ◽  
Terry G.J. Derks ◽  
...  
Keyword(s):  
Precision Medicine ◽  
Inborn Errors Of Metabolism ◽  
Diagnosis And Treatment ◽  
Inborn Errors ◽  
Complex Patterns

scholarly journals Detection of some metabolic disorders in suspected neonates admitted at Assiut University Children Hospital

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Shaimaa Mohamed Khalaf ◽  
Mohamed Mahrous El-Tellawy ◽  
Nafisa Hassan Refat ◽  
Amal Mohammed Abd El-Aal
Keyword(s):  
Inborn Errors Of Metabolism ◽  
Metabolic Disorders ◽  
Screening Program ◽  
The Body ◽  
Acid Oxidation ◽  
High Morbidity ◽  
Inborn Errors ◽  
Phenylalanine Level ◽  
Maple Syrup ◽  
Urea Cycle Defect

Abstract Background Inborn errors of metabolism are genetically inherited diseases which can lead to accumulation of toxic metabolites in the body. Inborn errors of metabolism have a high morbidity and mortality in neonates. Many inborn errors of metabolism are amenable to treatment with early diagnoses. Till now, more than 500 metabolic disorders have been detected. Although individual metabolic disorders are rare, the incidence of overall metabolic disorders is high. Results It was found that 70/200 cases (35 %) had confirmed inborn errors of metabolism, and another 8 cases (4%) suspected to have inborn errors of metabolism; 15/200 (7.5%) cases had mild elevation of phenylalanine level, while 107/200 (53.5%) had another diagnosis rather than metabolic disorders. Urea cycle defect was diagnosed in 20/70 (28.5%), maple syrup urine disease in 18/70 (25.7%), organic acidemia in 15/70 (21.4%), and non-ketotic hyperglycinemia in 1/70 (1.4 %) case. Also, 15/70 (21.4 %) cases had fatty acid oxidation defect. Lastly, one female case (1.4 %) was diagnosed to have disorder of pyrimidine deficiency. Conclusion Diagnosis of inborn errors of metabolism was confirmed in 35% of neonates, and 4% was suspected to have metabolic disorders. These results showed that inherited metabolic disorders are not rare. The development of a nationwide screening program for metabolic disorders is mandatory for early detection of these potentially treatable disorders.

scholarly journals Trends of congenital hypothyroidism and inborn errors of metabolism in Pakistan

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Sumreena Mansoor
Keyword(s):  
Congenital Hypothyroidism ◽  
Neonatal Intensive Care ◽  
Inborn Errors Of Metabolism ◽  
Metabolic Disorders ◽  
Genetic Disorders ◽  
Population Based ◽  
Preventive Strategy ◽  
Main Body ◽  
Inborn Errors ◽  
Mortality And Morbidity

Abstract Background Metabolic disorders are heterogeneous group of genetic disorders that are responsible for significant neonatal and infant morbidity and mortality worldwide. In developing countries like Pakistan where infant mortality is high current population based studies are unable to gauge contribution of metabolic disorders in causing mortality and morbidity. It is essential to address this gap by a review of available scattered Pakistani data related to metabolic disorders specifically congenital hypothyroidism and inborn error of metabolism to calculate probable burden of these disorders. Main body Unfortunately currently in Pakistan newborn screening which identifies these illnesses at birth as a preventive strategy are not available. For current review data was collected through a systematic search of published articles (including data related to screening in certain subgroups of patients admitted to pediatric/neonatal intensive care units, patients with developmental delay/mental retardation). Conclusion The primary aim of this review was to get an estimate of the disease burden in the Pakistani population as true prevalence of Congenital Hypothyroidism and Inborn Errors of Metabolism in Pakistan is not available. This systematic review will help us to identify the rough idea about the scale of problem in Pakistan.

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