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

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhuwen Gong ◽  
Lili Liang ◽  
Wenjuan Qiu ◽  
Huiwen Zhang ◽  
Jun Ye ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Dehydrogenase Deficiency ◽  
Disease Onset ◽  
Chinese Patients ◽  
Gas Chromatography Mass Spectrometry ◽  
Inherited Metabolic Disorder ◽  
Medium Chain ◽  
Chain Acyl ◽  
Generation Sequencing ◽  
Biochemical Abnormalities

ObjectiveMedium-chain acyl-CoA dehydrogenase deficiency (MCADD) is a rare inherited metabolic disorder of fatty acid β-oxidation. The present study aimed to evaluate clinical and biochemical manifestations, and the mutation spectrum of this disorder in a large cohort of Chinese patients.MethodsA total of 24 patients were enrolled, and blood acylcarnitine and urinary organic acid levels were measured by tandem mass spectrometry and gas chromatography–mass spectrometry (GC–MS), respectively. Mutations in the ACADM gene were detected by Sanger or next-generation sequencing. Clinical progression, acylcarnitine spectra, and mutations were analyzed and described in detail.ResultsAmong the 24 patients, six cases were diagnosed because of disease onset with symptoms such as vomiting, diarrhea, convulsion, and hypoglycemia; 18 patients without symptoms were diagnosed by newborn screening (NBS). All patients who accepted treatment after diagnosis developed normal intelligence and physique. The concentrations of octanoylcarnitine, the octanoylcarnitine/decanoylcarnitine ratio, and the octanoylcarnitine/acetylcarnitine ratio in the blood and urinary dicarboxylic acid concentrations were consistently elevated. Blood biomarkers failed to decrease after treatment. DNA sequencing revealed seven known and 17 novel mutations in the ACADM gene of patients. Mutation p.T150Rfs∗4 was most frequent, followed by p.R31C, p.F103Y, p.I223T, p.G362E, and c.387+1delG.ConclusionDespite biochemical abnormalities, medium-chain acyl-CoA dehydrogenase deficiency showed relatively mild clinical phenotypes with low mortality and optimistic prognoses in China. NBS is crucial for early diagnosis, treatment, and prognosis.

When Do Gut Flora in the Newborn Produce 3-Phenylpropionic Acid? Implications for Early Diagnosis of Medium-Chain Acyl-CoA Dehydrogenase Deficiency

1992 ◽  
Vol 38 (2) ◽  
pp. 278-281 ◽  
Author(s):  
Michael J Bennett ◽  
Ajay Bhala ◽  
Stephanie F Poirier ◽  
Marie C Ragni ◽  
Steven M Willi ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Isotope Dilution Mass Spectrometry ◽  
Bacterial Metabolism ◽  
Gas Chromatography Mass Spectrometry ◽  
Mcad Deficiency ◽  
Phenylpropionic Acid ◽  
Medium Chain ◽  
Stable Isotope Dilution ◽  
Significant Difference ◽  
Chain Acyl

Abstract Urinary excretion of 3-phenylpropionylglycine (PPG) is a diagnostic marker for medium-chain acyl-CoA dehydrogenase (MCAD) deficiency. PPG is derived from 3-phenylpropionic acid (PPA), a product of anaerobic bacterial metabolism in the gut. To determine when the infant gut was colonized with PPA-producing bacteria, we cultured stool in prereduced thioglycollate broth from 93 apparently healthy infants. We analyzed the products of bacterial metabolism by gas chromatography/mass spectrometry for the presence of PPA. Trend analysis demonstrated a significant difference (P less than 0.001) in PPA production between early and later infancy. PPA was not detected in 84% of media isolated from stool collected from infants younger than four months. For older infants, 67% of the samples were PPA-positive. Thus, because the normal gut is not sufficiently colonized with PPA-producing bacteria before three to four months of age, PPG analysis alone is not a sensitive marker for the early detection of MCAD deficiency. Using stable isotope dilution mass spectrometry, we measured PPG and n-hexanoylglycine (HG) excretion in two well newborns with MCAD deficiency. HG, believed to be an endogenous metabolite associated with MCAD deficiency, was consistently above normal in all urine samples.

(omega-1)-Hydroxymonocarboxylic acids in urine of infants fed medium-chain triglycerides.

1981 ◽  
Vol 27 (10) ◽  
pp. 1661-1664 ◽  
Author(s):  
Y Shigematsu ◽  
T Momoi ◽  
M Sudo ◽  
Y Suzuki
Keyword(s):  
Mass Spectrometry ◽  
Fatty Acids ◽  
Octanoic Acid ◽  
Monocarboxylic Acid ◽  
Decanoic Acid ◽  
Gas Chromatography Mass Spectrometry ◽  
Medium Chain Triglycerides ◽  
Medium Chain ◽  
Chain Acyl ◽  
Total Fatty Acids

Abstract Organic acids in the urine of infants fed a formula containing medium-chain triglycerides (octanoic acid 49% and decanoic acid 26% of total fatty acids) were determined by gas chromatography-mass spectrometry. We found a considerable amount of 5-hydroxyhexanoic acid and 7-hydroxyoctanoic acid, but no detectable 9-hydroxydecanoic acid, as well as a large amount of C6-C10-dicarboxylic acid. We believe that such acids are derived, via (omega-1)-hydroxylation, from medium-chain monocarboxylic acid or medium-chain acyl-CoA in the liver cell. The degree of (omega-1)-hydroxylation of medium-chain fatty acids relative to omega-hydroxylation apparently increases as the chain length of the fatty acids decreases.

scholarly journals 2-Ethylhydracrylic Aciduria in Short/Branched-Chain Acyl-CoA Dehydrogenase Deficiency: Application to Diagnosis and Implications for the R-Pathway of Isoleucine Oxidation

2005 ◽  
Vol 51 (3) ◽  
pp. 610-617 ◽  
Author(s):  
Stanley H Korman ◽  
Brage S Andresen ◽  
Avraham Zeharia ◽  
Alisa Gutman ◽  
Avihu Boneh ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Dehydrogenase Deficiency ◽  
Direct Sequencing ◽  
Gene Mutations ◽  
Gas Chromatography Mass Spectrometry ◽  
Gene Encoding ◽  
Chain Acyl ◽  
Methylbutyric Acid ◽  
Branched Chain ◽  
Urine Organic Acids

Abstract Background: Isolated excretion of 2-methylbutyrylglycine (2-MBG) is the hallmark of short/branched-chain acyl-CoA dehydrogenase deficiency (SBCADD), a recently identified defect in the proximal pathway of l-isoleucine oxidation. SBCADD might be underdiagnosed because detection and recognition of urine acylglycines is problematic. Excretion of 2-ethylhydracrylic acid (2-EHA), an intermediate formed in the normally minor R-pathway of l-isoleucine oxidation, has not previously been described in SBCADD. Methods: Samples from four patients with 2-MBG excretion were analyzed by gas chromatography–mass spectrometry for urine organic acids, quantification of 2-MBG, and chiral determination of 2-methylbutyric acid. Blood-spot acylcarnitines were measured by electrospray–tandem mass spectrometry. Mutations in the ACADSB gene encoding SBCAD were identified by direct sequencing. Results: SBCADD was confirmed in each patient by demonstration of different ACADSB gene mutations. In multiple urine samples, organic acid analysis revealed a prominent 2-EHA peak usually exceeding the size of the 2-MBG peak. Approximately 40–46% of total 2-methylbutyric acid conjugates were in the form of the R-isomer, indicating significant metabolism via the R-pathway. Conclusions: If, as generally believed, SBCAD is responsible for R-2-MBG dehydrogenation in the R-pathway, 2-EHA would not be produced in SBCADD. Our observation of 2-ethylhydracrylic aciduria in SBCADD implies that a different or alternative enzyme serves this function. Increased flux through the R-pathway may act as a safety valve for overflow of accumulating S-pathway metabolites and thereby mitigate the severity of SBCADD. Awareness of 2-ethylhydracrylic aciduria as a diagnostic marker could lead to increased detection of SBCADD and improved definition of its clinical phenotype.

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