Clinical, Biochemical, and Molecular Analyses of Medium-Chain Acyl-CoA Dehydrogenase Deficiency in Chinese Patients

Gong, Zhuwen; Liang, Lili; Qiu, Wenjuan; Zhang, Huiwen; Ye, Jun; Wang, Yu; Ji, Wenjun; Chen, Ting; Gu, Xuefan; Han, Lianshu

doi:10.3389/fgene.2021.577046

Cited by 10 publications

(5 citation statements)

References 20 publications

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“…Suberic acid, a dicarboxylic acid, is present in the urine of individuals with fatty acid oxidation disorders. Elevated levels are found in individuals with medium-chain acyl-CoA dehydrogenase deficiency [ 42 ]. It is also associated with carnitine-acylcarnitine translocase deficiency, malonyl-Coa decarboxylase deficiency.…”

Section: Discussionmentioning

confidence: 99%

Urinary metabolomics using gas chromatography-mass spectrometry: potential biomarkers for autism spectrum disorder

Chand¹,

Majid²,

Ahmed³

et al. 2022

BMC Neurol

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Background Diagnosis of autism spectrum disorder (ASD) is generally made phenotypically and the hunt for ASD-biomarkers continues. The purpose of this study was to compare urine organic acids profiles of ASD versus typically developing (TD) children to identify potential biomarkers for diagnosis and exploration of ASD etiology. Methods This case control study was performed in the Department of Pathology and Laboratory Medicine in collaboration with the Department of Pediatrics and Child Health, Aga Khan University, Pakistan. Midstream urine was collected in the first half of the day time before noon from the children with ASD diagnosed by a pediatric neurologist based on DSM-5 criteria and TD healthy controls from August 2019 to June 2021. The urine organic acids were analyzed by Gas Chromatography-Mass Spectrometry. To identify potential biomarkers for ASD canonical linear discriminant analysis was carried out for the organic acids, quantified in comparison to an internal standard. Results A total of 85 subjects were enrolled in the current study. The mean age of the ASD (n = 65) and TD groups (n = 20) was 4.5 ± 2.3 and 6.4 ± 2.2 years respectively with 72.3% males in the ASD group and 50% males in the TD group. Parental consanguinity was 47.7 and 30% in ASD and TD groups, respectively. The common clinical signs noted in children with ASD were developmental delay (70.8%), delayed language skills (66.2%), and inability to articulate sentences (56.9%). Discriminant analysis showed that 3-hydroxyisovalericc, homovanillic acid, adipic acid, suberic acid, and indole acetic were significantly different between ASD and TD groups. The biochemical classification results reveal that 88.2% of cases were classified correctly into ASD& TD groups based on the urine organic acid profiles. Conclusion 3-hydroxy isovaleric acid, homovanillic acid, adipic acid, suberic acid, and indole acetic were good discriminators between the two groups. The discovered potential biomarkers could be valuable for future research in children with ASD.

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Section: Discussionmentioning

confidence: 99%

Urinary metabolomics using gas chromatography-mass spectrometry: potential biomarkers for autism spectrum disorder

Chand¹,

Majid²,

Ahmed³

et al. 2022

BMC Neurol

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“…13 Sudden death has historically been the first manifestation of prior to the onset of illness. 2,13,16,17 Arrhythmias can be induced by the accumulation of mediumchain acylcarnitines in MCADD, particularly in infancy. In neonatal cases, prolongation of the QT interval has also been reported.…”

Section: Clinic Al Pre S Entationmentioning

confidence: 99%

“…Sudden death has historically been the first manifestation of MCADD in a portion of patients; up to 25% of MCADD‐affected individuals will die during their first clinical manifestation of the condition. MCADD is an established cause of sudden infant death syndrome; this is most common when infants display no defining features of MCADD or receive normal newborn screening results prior to the onset of illness 2,13,16,17 …”

Section: Clinical Presentationmentioning

confidence: 99%

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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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“…Moreover, this missense variant is predicted to be probably damaging, with a score of 0.979, by PolyPhen2 ( http://genetics.bwh.harvard.edu/pph2/ ) and deleterious, with scores of −8.147 and −5.25173, by PROVEAN ( http://provean.jcvi.org/index.php/ ) and PANTHER ( http://www.pantherdb.org/tools/csnpScoreForm.jsp/ ), respectively. Although c.1040G > T has very recently been reported as a novel variant observed in 1 of 24 Chinese patients with MCADD 9 , no detailed assessment was performed to classify the pathogenicity of this variant with evidence according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) guidelines 10 . This missense variant is absent in the population database (PM2); it may cause a deleterious effect on the gene product, as supported by multiple lines of computational evidence (PP3).…”

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confidence: 99%

MCAD deficiency caused by compound heterozygous pathogenic variants in ACADM

et al. 2022

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Medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency is an autosomal recessive disease caused by biallelic pathogenic ACADM variants. We report a case of an asymptomatic Japanese girl with MCAD deficiency caused by compound heterozygous pathogenic variants (NM_000016.5:c.1040G > T (p.Gly347Val) and c.449_452delCTGA (p.Thr150ArgfsTer4)). Because the MCAD residual activity in lymphocytes of the patient was below the limit of quantification, both variants are likely to cause complete loss of MCAD enzymatic activity.

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Clinical, Biochemical, and Molecular Analyses of Medium-Chain Acyl-CoA Dehydrogenase Deficiency in Chinese Patients

Cited by 10 publications

References 20 publications

Urinary metabolomics using gas chromatography-mass spectrometry: potential biomarkers for autism spectrum disorder

Urinary metabolomics using gas chromatography-mass spectrometry: potential biomarkers for autism spectrum disorder

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

MCAD deficiency caused by compound heterozygous pathogenic variants in ACADM

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