Development of a Tandem Mass Spectrometry Method for Rapid Measurement of Medium- and Very-Long-Chain Acyl-CoA Dehydrogenase Activity in Fibroblasts

Bouvier, Damien; Vianey‐Saban, Christine; Ruet, Séverine; Acquaviva, Cécile

doi:10.1007/8904_2016_22

Cited by 10 publications

(6 citation statements)

References 13 publications

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“…On the other hand, in the case of symptomatic VLCADD patient, the homozygous mutation c. 1500_1502del (p.Leu502del) was already reported in literature in a patient of 9 years with exercise intolerance with cramps and myoglobinuria triggered by fasting and cold and residual activity in fibroblast of VLCAD of 7% [ 28 ]. Our patient with the same mutation and a clinical history of recurrent episodes of rhabdomyolysis in his first two decades of life, had residual activity of 5%, supporting this genotype-phenotype correlation.…”

Section: Discussionmentioning

confidence: 99%

Diagnosis, genetic characterization and clinical follow up of mitochondrial fatty acid oxidation disorders in the new era of expanded newborn screening: A single centre experience

Maguolo

Rodella

Dianin

et al. 2020

Molecular Genetics and Metabolism Reports

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Introduction Mitochondrial fatty acid oxidation disorders (FAODs) are a heterogeneous group of hereditary autosomal recessive diseases included in newborn screening (NBS) program in Italy. The aim of this study was to analyse FAODs cases, identified either clinically or by NBS,for clinical and genetic characterization and to evaluate a five years' experience of NBS, in the attempt to figure out the complexity of genotype-phenotype correlation and to confirm the clinical impact of NBS in our centre experience. Materials and methods We analysed FAODs patients diagnosed either by NBS or clinically, followed since February 2014 to April 2019 at the Regional Screening Centre and Inherited Metabolic Diseases Unit of Verona. Diagnosis was confirmed by plasma acylcarnitines, urinary organic acids, enzymatic and genetic testing. For not clear genotypes due to the presence of variants of uncertain significance, in silico predictive tools have been used as well as enzymatic activity assays. Patients underwent clinical, nutritional and biochemical follow up. Results We diagnosed 30 patients with FAODs. 20 by NBS: 3 CUD, 6 SCADD, 5 MCADD, 4 VLCADD, 2 MADD. Overall incidence of FAODs diagnosed by NBS was 1:4316 newborns. No one reported complications during the follow up period. 10 patients were diagnosed clinically: 2 CUD, 2 CPT2D, 1 VLCADD, 5 MADD. Mean age at diagnosis was 29.3 years. Within this group, complications or symptoms were reported at diagnosis, but not during follow-up. 12 mutations not previously reported in literature were found, all predicted as pathogenic or likely pathogenic. Discussion and conclusions Our study highlighted the great phenotypic variability and molecular heterogeneity of FAODs and confirmed the importance of a tailored follow up and treatment. Despite the short duration of follow up, early identification by NBS prevented diseases related complications and resulted in normal growth and psycho-motor development as well.

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Section: Discussionmentioning

confidence: 99%

Diagnosis, genetic characterization and clinical follow up of mitochondrial fatty acid oxidation disorders in the new era of expanded newborn screening: A single centre experience

Maguolo

Rodella

Dianin

et al. 2020

Molecular Genetics and Metabolism Reports

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“…Definitive diagnosis of MCADD requires sequencing of the ACADM gene for identification of mutations, as well as reduced MCAD activity in patient fibroblasts as determined through LC-MS/MS, typically ranging between 10% and 35% of regular enzyme activity. 30,31 Prenatal sequencing is possible in the case of maternal MCADD.…”

Section: Molecular Genetic Sequencing In Diagnosticsmentioning

confidence: 99%

Medium‐chain Acyl‐COA dehydrogenase deficiency: Pathogenesis, diagnosis, and treatment

Mason

Hindmarch

Dunham‐Snary

2022

Endocrino Diabet & Metabol

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Introduction Medium‐Chain Acyl‐CoA Dehydrogenase Deficiency (MCADD) is the most common inherited metabolic disorder of β‐oxidation. Patients with MCADD present with hypoketotic hypoglycemia, which may quickly progress to lethargy, coma, and death. Prognosis for MCADD patients is highly promising once a diagnosis has been established, though management strategies may vary depending on the severity of illness and the presence of comorbidities. Methods and Results Given the rapid developments in the world of gene therapy and implementation of newborn screening for inherited metabolic disorders, the provision of concise and contemporary knowledge of MCADD is essential for clinicians to effectively manage patients. Thus, this review aims to consolidate current information for physicians on the pathogenesis, diagnostic tools, and treatment options for MCADD patients. Conclusion MCADD is a commonly inherited metabolic disease with serious implications for health outcomes, particularly in children, that may be successfully managed with proper intervention.

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“…There is a correlation between genotype and acylcarnitine levels, with an overlap in increased concentrations of C8 in carriers and affected with moderate levels [ 65 , 66 ]. In these cases, enzyme activity assays and very careful genetic studies could be used for diagnosis, mostly via newborn screening [ 67 ]. The typical and diagnostic values found in MCAD are as follows:…”

Section: Study Of Metabolites In the Diagnosis Of Fatty Acid Oxidation Defectsmentioning

confidence: 99%

Biochemical Markers for the Diagnosis of Mitochondrial Fatty Acid Oxidation Diseases

Ruíz-Sala

Quintana

2021

JCM

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Mitochondrial fatty acid β-oxidation (FAO) contributes a large proportion to the body’s energy needs in fasting and in situations of metabolic stress. Most tissues use energy from fatty acids, particularly the heart, skeletal muscle and the liver. In the brain, ketone bodies formed from FAO in the liver are used as the main source of energy. The mitochondrial fatty acid oxidation disorders (FAODs), which include the carnitine system defects, constitute a group of diseases with several types and subtypes and with variable clinical spectrum and prognosis, from paucisymptomatic cases to more severe affectations, with a 5% rate of sudden death in childhood, and with fasting hypoketotic hypoglycemia frequently occurring. The implementation of newborn screening programs has resulted in new challenges in diagnosis, with the detection of new phenotypes as well as carriers and false positive cases. In this article, a review of the biochemical markers used for the diagnosis of FAODs is presented. The analysis of acylcarnitines by MS/MS contributes to improving the biochemical diagnosis, both in affected patients and in newborn screening, but acylglycines, organic acids, and other metabolites are also reported. Moreover, this review recommends caution, and outlines the differences in the interpretation of the biomarkers depending on age, clinical situation and types of samples or techniques.

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Development of a Tandem Mass Spectrometry Method for Rapid Measurement of Medium- and Very-Long-Chain Acyl-CoA Dehydrogenase Activity in Fibroblasts

Cited by 10 publications

References 13 publications

Diagnosis, genetic characterization and clinical follow up of mitochondrial fatty acid oxidation disorders in the new era of expanded newborn screening: A single centre experience

Diagnosis, genetic characterization and clinical follow up of mitochondrial fatty acid oxidation disorders in the new era of expanded newborn screening: A single centre experience

Medium‐chain Acyl‐COA dehydrogenase deficiency: Pathogenesis, diagnosis, and treatment

Biochemical Markers for the Diagnosis of Mitochondrial Fatty Acid Oxidation Diseases

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