Iron deficiency anemia is a common disorder during infancy and childhood. Medium chain acyl-CoA dehydrogenase (MCAD) deficiency is the most common disorder of mitochondrial fatty acid oxidation. However, this metabolic disorder is extremely rare among Asians. Generally MCAD deficiency patients are healthy until initial presentation of hypoketogenic hypoglycemia and encephalopathy which is predisposed by an intercurrent illness and/or a period of poor oral intake. The first attack causes a high risk of mortality or permanent neurologic sequelae. The authors report a suspect case of MCAD deficiency with iron deficiency anemia, with a brief review of related literatures.
Acyl-CoA Dehydrogenase* ; Anemia, Iron-Deficiency* ; Asian Continental Ancestry Group ; Humans ; Hypoglycemia ; Iron* ; Mortality

OBJECTIVE: To explore the clinical and genetic characteristics of four patients with medium-chain acyl-CoA dehydrogenase deficiency (MCADD). METHODS: Four children who had presented at the Children's Hospital Affiliated to Zhengzhou University between August 2019 and August 2021 were selected as the study subjects. Clinical data of the children were collected. The children were subjected to whole exome sequencing (WES). RESULTS: All of the four children were diagnosed with MCADD. Blood amino acid and ester acyl carnitine spectrum test showed that the concentration of octanoyl carnitine (C8) was significantly increased. The main clinical manifestations included poor mental response (3 cases), intermittent diarrhea with abdominal pain (1 case), vomiting (1 case), increased transaminase (3 cases), and metabolic acidosis (2 cases). Five variants were identified by genetic testing, among which c.341A>G (p.Y114C) was unreported previously. Three were missense variants, one was frameshift variant and one was splicing variant. CONCLUSION The clinical heterogeneity of MCADD is obvious, and the severity of the disease may vary. WES can assist with the diagnosis. Delineation of the clinical symptoms and genetic characteristics of the disease can facilitate early diagnosis and treatment of the disease.
Child ; Humans ; Acyl-CoA Dehydrogenase/genetics* ; Carnitine ; Genetic Testing ; Lipid Metabolism, Inborn Errors/genetics* ; Neonatal Screening

OBJECTIVES: To investigate the genotypes and biochemical phenotypes of neonates with abnormal metabolism of butyrylcarnitine (C4). METHODS: One hundred and twenty neonates with increased C4 levels detected by tandem mass spectrometry in the neonatal screening at Children's Hospital, Zhejiang University School of Medicine from January 2018 to June 2023 were included. The initial screening data and recalled data of C4 and C4/C3 were collected and converted into multiples of C4 reference range. Next generation sequencing was performed and the exons with adjacent 50 bp regions of ACAD8 and ACADS genes were captured by liquid phase capture technique. Variant information was obtained by bioinformatic analysis and the pathogenicity were classified according to the American College of Medical Genetics and Genomics criteria. The Wilcoxon rank sum test was used to analyze the differences in C4 levels among neonates with different variation types. RESULTS: In total, 32 variants in ACAD8 gene were detected, of which 7 variants were reported for the first time; while 41 variants of ACADS gene were detected, of which 17 variants have not been previously reported. There were 39 cases with ACAD8 biallelic variations and 3 cases with ACAD8 monoallelic variations; 34 cases with ACADS biallelic variations and 36 cases with ACADS monoallelic variations. Furthermore, 5 cases were detected with both ACAD8 and ACADS gene variations. Inter group comparison showed that the multiples of C4 reference range in initial screening and re-examination of the ACAD8 biallelic variations and ACADS biallelic variations groups were significantly higher than those of the ACADS monoallelic variations group (all P<0.01), while the multiples in the ACAD8 biallelic variations group were significantly higher than those in the ACADS biallelic variations group (all P<0.01). The multiples of C4 reference range in the initial screening greater than 1.5 times were observed in all neonates carrying ACAD8 or ACADS biallelic variations, while only 25% (9/36) in neonates carrying ACADS monoallelic variations. CONCLUSIONS ACAD8 and/or ACADS gene variants are the main genetic causes for elevated C4 in newborns in Zhejiang region with high genotypic heterogeneity. The C4 levels of neonates with biallelic variations are significantly higher than those of neonates with monoallelic variations. The cut-off value for C4 level could be modestly elevated, which could reduce the false positive rate in tandem mass spectrometry neonatal screening.
Child ; Humans ; Infant, Newborn ; Acyl-CoA Dehydrogenase/genetics* ; Genotype ; Phenotype ; Carnitine/metabolism* ; Mutation

Since we started organic acid analysis in July 1997, we have collected data about organic acidemias in Korea. The data presented herein constitute our 3 years experience in organic acid analysis. We have collected 712 samples from major university hospitals in all over Korea, which are large enough for relatively accurate estimation of incidence of organic acid disorders. We used solvent extraction method with ethylacetate, MSTFA for derivatization and simultaneously quantitation of 83 organic acids. Out of 712 patients sample, 498 samples (70%) showed no evidence of organic acid abnormalities. Out of the 214 remaining samples, we found very diverse disorders such as methylmalonic aciduria (6), propionic aciduria (10), biotinidase deficiency (6), maple syrup urine disease (3), isovaleric aciduria (4), tyrosinemia type II (4), tyrosinemia type IV (1), glutaric aciduria type I (1), glutaric aciduria type II (22), 3-methylglutaconic aciduria type I (3), 3-methylglutaconic aciduria type III (7), HMG-CoA lyase deficiency (1), hyperglyceroluria (2), cytosolic 3-ketothiolase deficiency (55), mitochondrial 3-ketothiolase deficiency (3), 3-hydroxyisobutyric aciduria (2), L-2-hydroxyglutaric aciduria (2), fumaric aciduria (2), lactic aciduria with combined elevation of pyruvate (most likely PDHC deficiency) (28), lactic aciduria without combined elevation of pyruvate (most likely mitochondrial respiratory chain disorders) (35), SCAD deficiency (3), MCAD deficiency (1), 3-methylcrotonylglycineuria (1), orotic aciduria (most likely urea cycle disorders) (7) and 2-methylbranched chain acyl-CoA dehydrogenase deficiency (1). In conclusion, although the incidence of individual organic acidemia is low, the incidence of overall organic acidemia is relatively high in Korea. Most of the patients showed some signs of neurological dysfunction. Therefore, organic acid analysis should be included in the diagnostic work up of all neurological dysfunctions.
Acetyl-CoA C-Acyltransferase ; Acyl-CoA Dehydrogenase ; Biotinidase Deficiency ; Cytosol ; Electron Transport ; Hospitals, University ; Humans ; Incidence ; Korea* ; Maple Syrup Urine Disease ; Multiple Acyl Coenzyme A Dehydrogenase Deficiency ; Propionic Acidemia ; Pyruvic Acid ; Tyrosinemias ; Urea

OBJECTIVE: To analyze the clinical features and genetic variants in four neonates with very long chain acyl-coenzyme A dehydrogenase (VLCAD) deficiency. METHODS: Neonates with a tetradecenoylcarnitine (C14:1) concentration at above 0.4 μmol/L in newborn screening were recalled for re-testing. Four neonates were diagnosed with VLCAD deficiency by MS-MS and genetic testing, and their clinical features and genotypes were analyzed. RESULTS: All cases had elevated blood C14:1, and the values of first recalls were all lower than the initial test. In 2 cases, the C14:1 had dropped to the normal range. 1 case has remained at above 1 μmol/L after the reduction, and the remainder one case was slightly decreased. In total eight variants of the ADACVL genes were detected among the four neonates, which included 5 missense variants and 3 novel variants (p.Met344Val, p.Ala416Val, c.1077+6T>A). No neonate showed salient clinical manifestations. CONCLUSION Above findings have enriched the spectrum of ADACVL gene mutations and provided a valuable reference for the screening and diagnosis of VLCAD deficiency.
Acyl-CoA Dehydrogenase/genetics* ; Acyl-CoA Dehydrogenase, Long-Chain ; Congenital Bone Marrow Failure Syndromes ; Genetic Testing ; Humans ; Infant, Newborn ; Lipid Metabolism, Inborn Errors ; Mitochondrial Diseases ; Muscular Diseases ; Tandem Mass Spectrometry

During epididymal transit, mammalian spermatozoa acquire new surface proteins that are necessary for gamete interaction. P34H, a member of the short-chain dehydrogenase/reductase(SDR) superfamily, is acquired on the acrosomal cap of human spermatozoon during its maturation arising within epididymis. P34H has been shown to be involved in sperm-zona pellucida interaction. Research revealed that the occurrence of low concentration of sperm protein P34H were significant amongst the idiopathic infertile male population and P34H protein could also be considered as a marker of epididymal sperm maturation in human. Therefore the level of sperm protein P34H is proposed to be a auxiliary diagnostic tool for male infertility. This paper reviews the molecular properties and regulation of the expression of P34H and its association with male reproduction.
Acyl-CoA Dehydrogenase ; Fatty Acid Desaturases ; chemistry ; Gene Expression ; Humans ; Male ; Proteins ; genetics ; physiology ; Sperm Maturation ; physiology ; Sugar Alcohol Dehydrogenases

A boy aged 6 years and 3 months developed upper respiratory tract infection and pyrexia 2 months ago and was given oral administration of nimesulide by his parents according to directions. Half an hour later, the boy experienced convulsions and cardiopulmonary arrest, and emergency examination found hypoketotic hypoglycemia, metabolic acidosis, significant increases in serum aminotransferases and creatine kinase, and renal damage. Recovery of consciousness and vital signs was achieved after cardiopulmonary resuscitation, but severe mental and movement regression was observed. The boy had a significant reduction in free carnitine in blood and significant increases in medium- and long-chain fatty acyl carnitine, urinary glutaric acid, 3-hydroxy glutaric acid, isovalerylglycine, and ethylmalonic acid, suggesting the possibility of multiple acyl-CoA dehydrogenase deficiency. After the treatment with vitamin B2, L-carnitine, and bezafibrate, the boy gradually improved, and reexamination after 3 months showed normal biochemical parameters. The boy had compound heterozygous mutations in the ETFDH gene, i.e., a known mutation, c.341G>A (p.R114H), from his mother and a novel mutation, c.1484C>G (p.P495R), from his father. Finally, he was diagnosed with multiple acyl-CoA dehydrogenase deficiency. Reye syndrome and sudden death symptoms were caused by nimesulide-induced acute metabolic crisis. It is concluded that inherited metabolic diseases may be main causes of Reye syndrome and sudden death, and biochemical and genetic analyses are the key to identifying underlying diseases.
Acyl-CoA Dehydrogenase ; Administration, Oral ; Carnitine ; Child ; Death, Sudden ; Humans ; Male ; Respiratory Tract Infections ; Reye Syndrome ; Sulfonamides

OBJECTIVE: To investigate the effect of medium-chain acyl-CoA dehydrogenase (ACADM) on invasion and metastasis of breast cancer cells and explore the underlying mechanism. METHODS: A large cancer genome database was used to analyze the expression of ACADM in breast cancer tissues and normal tissues. The proliferation, migration and invasion of cultured breast cancer MCF-7 and T47D cells with ACADM overexpression or ACADM silencing were evaluated using MTT proliferation assay, EdU assay, Transwell chamber assay, and Boyden invasion assay; Western blotting was used to detect the protein expressions of the related pathway in the cells. In nude mouse models of tail vein metastasis of MCF-7 cells with or without ACADM overexpression, the tumor growth and tumor histopathology were observed using HE staining. RESULTS: Analysis of the Oncomine sample set showed a significantly higher expression level of ACADM in breast cancer tissues than in normal breast tissues ( < 0.05). Overexpression of ACADM obviously enhanced the migration and invasion abilities and promoted the epithelial-mesenchymal transition (EMT) of cultured MCF-7 and T47D cells; conversely, silencing of ACADM significantly suppressed the migration and invasion of the breast cancer cells. In the nude mouse models, ACADM overexpression in MCF-7 cells significantly enhanced their migration and invasion abilities. CONCLUSIONS ACADM can promote the EMT process of breast cancer cells and improve the migration and invasion ability. ACADM is an oncogene in breast cancer.
Acyl-CoA Dehydrogenase ; Animals ; Breast Neoplasms ; Cell Movement ; Cell Proliferation ; Epithelial-Mesenchymal Transition ; Humans ; MCF-7 Cells ; Mice

The purpose of this study was to discern the critical point in skeletal muscle fatty acid oxidation by changing plasma free fatty acids (FFA) level in rat. In the study, 3 key steps in lipid oxidation were examined after changing plasma FFA level by acipimox. The rates of both palmitate and palmitoyl- carnitine oxidation were decreased by decrease of plasma FFA level, however, carnitine palmitoyl transferase (CPT) 1 activity was not changed, suggesting CPT1 activity may not be involved in the fatty acid oxidation at the early phase of plasma FFA change. In the fasted rats, beta-hydroxy acyl-CoA dehydrogenase (beta-HAD) activity was depressed to a similar extent as palmitate oxidation by a decrease of plasma FFA level. This suggested that beta-oxidation might be an important process to regulate fatty acid oxidation at the early period of plasma FFA change. Citrate synthase activity was not altered by the change of plasma FFA level. In conclusion, the critical step in fatty acids oxidation of skeletal muscles by the change of plasma FFA level by acipimox in fasting rats might be the beta-oxidation step rather than CPT1 and TCA cycle pathways.
Acyl-CoA Dehydrogenase ; Animals ; Carnitine ; Citrate (si)-Synthase ; Fasting ; Fatty Acids ; Fatty Acids, Nonesterified* ; Muscle, Skeletal ; Plasma* ; Rats* ; Transferases

PURPOSE: We have done this retrospective study to know the relative incidences and clinical manifestations of organic acidopathies in Korea. METHODS: The results of quantitative organic acid analysis of 1,125 samples of 712 patients, referred from Jul. 1997 to Jun. 2000, were analyzed retrospectively according to four age groups (-2 mon, 3 mon-2 year, 3 years-12 years, over 12 years) and major clinical manifestations. Quantification of 83 organic acids was done with gas chromatography and mass spectrometry(GC/MS). RESULTS: We diagnosed 214 patients with 27 diseases of organic acid metabolism during this study period. Diseases found more than 10 cases are cytosolic 3-ketothiolase deficiency, mitochondrial repsiratory chain disorders, PDHC deficiency, glutaric aciduria type II and propionic aciduria. Other diseases were diagnosed in less than 10 cases, mostly one or two cases during this study period. Most of the patients had some symptoms of neurological dysfunction such as seizure activity(195 patients), developmental delay(122), mental retardation(99), hypotonia(84), movement disorders(81) and vomiting(68). CONCLUSION: Though the incidence of individual organic acidemia is low, the overall incidence of organic acidemia as a whole seems to be relatively high in Korea. Most of the patients showed some signs of neurological dysfunction.
Acetyl-CoA C-Acyltransferase ; Chromatography, Gas ; Cytosol ; Humans ; Incidence ; Korea* ; Metabolism ; Multiple Acyl Coenzyme A Dehydrogenase Deficiency ; Propionic Acidemia ; Pyruvate Dehydrogenase Complex Deficiency Disease ; Retrospective Studies ; Seizures