OBJECTIVE: To elucidate the epidemiological characteristics and genetic variant profile of Short-chain acyl-CoA dehydrogenase deficiency (SCADD) among newborns from Hainan Province and evaluate its significance within the local neonatal disease screening panel. METHODS: A total of 84 184 newborns born in Hainan Province from February to December 2024 were included. Tandem mass spectrometry (MS/MS) was employed to detect butyrylcarnitine (C4) and propionylcarnitine (C3) levels in dried blood spots. Screening thresholds were set at C4 > 0.43 μ mol/L and C4/C3 ratio > 0.28. Suspected cases underwent confirmatory testing via urinary ethylmalonic acid analysis by gas chromatography-mass spectrometry and whole-exome sequencing for ACADS gene variants. This study was approved by the Medial Ethics Committee of the hospital (Ethics No.: HNWCMC-2024-55). RESULTS: Six SCADD cases (male-to-female ratio = 1:1) were diagnosed, with all carrying compound heterozygous variants at two loci, yielding a prevalence of 7.13 per 100,000 live births. Four known ACADS gene variants were identified, with both c.322G>A and c.625G>A detected at a frequency of 41.7%. Regular follow-up (as of January 2026) revealed that all diagnosed cases have remained asymptomatic with normal growth and development. CONCLUSION The prevalence of SCADD among newborns in Hainan Province is relatively high, with c.322G>A and c.625G>A as the hotspot variants in the region. Given the absence of clinical phenotypes in all screen-detected cases during long-term follow-up, it is recommended to remove this condition from the routine neonatal screening program for this region to reduce unnecessary anxiety and medical cost.
Humans ; Infant, Newborn ; Neonatal Screening/methods* ; Female ; Male ; Lipid Metabolism, Inborn Errors/epidemiology* ; Acyl-CoA Dehydrogenase/genetics* ; China/epidemiology* ; Follow-Up Studies

OBJECTIVE: To explore the genetic basis of a child with Chanarin-Dorfman syndrome (CDS) manifesting as ichthyosis. METHODS: A child who had presented at Henan Provincial People's Hospital in June 2023 was selected as study subject. Clinical data of the child was collected. Peripheral blood samples were collected from the child and her parents. Following extraction of genomic DNA, whole-exome sequencing (WES) was carried out. Candidate variants were verified by Sanger sequencing. Relevant literature was searched in databases using key words "Chanarin-Dorfman syndrome" and "ABHD5 gene". The clinical manifestations and variant sites of previously reported cases were compiled and analyzed for correlations. This study was approved by the Medical Ethics Committee of Henan Provincial People's Hospital [Ethics No.: (2019) Jun Shen No. (134)]. RESULTS: WES revealed that the child has harbored compound heterozygous variants of the ABHD5 gene, namely c.99_103del (p.H34*) in exon 2 and c.770C>G (p.P257R) in exon 5, which were inherited from her father and mother, respectively. Bioinformatic analysis suggested that both variants were pathogenic. Literature review indicated that the affected organs in CDS are ranked from most to least including liver, eyes, ears, nervous system, muscles, spleen, and kidneys. The c.594insC and c.594dupC variants are most common. CONCLUSION The identification of the two novel ABHD5 gene variants has enriched the mutation spectrum of CDS. c.594insC or c.594dupC are hotspot mutations of this disease, albeit with no definitive correlation between the genotype and phenotype.
Humans ; Female ; Ichthyosiform Erythroderma, Congenital/genetics* ; Lipid Metabolism, Inborn Errors/genetics* ; Phenotype ; 1-Acylglycerol-3-Phosphate O-Acyltransferase/genetics* ; Mutation ; Muscular Diseases/genetics* ; Exome Sequencing ; Child ; Male ; Child, Preschool

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

Humans ; Muscular Diseases/genetics* ; Cardiomyopathies/genetics* ; Lipid Metabolism, Inborn Errors/genetics* ; Mutation ; Lipids ; Muscle, Skeletal ; Acyltransferases/genetics* ; Lipase/genetics*

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

OBJECTIVE: To report on the clinical, metabolic and genetic characteristics of a child with carnitine palmitoyl transferase 1A (CPT1A) deficiency. METHODS: Clinical data and the level of acylcarnitine for a child who initially presented as epilepsy were analyzed. Genomic DNA was extracted from peripheral blood samples of the child and her parents and subjected to next-generation sequencing (NGS). RESULTS: Mass spectrometry of blood acylcarnitine indicated increased carnitine 0 (C0) and significantly increased C0/ (C16+C18). DNA sequencing revealed that the child has carried compound heterozygous variants of the CPT1A gene, namely c.1846G>A and c.2201T>C, which were respectively inherited from her mother and father. CONCLUSION CPT1A presenting initially as epilepsy was unreported previously. Analysis of blood acylcarnitine C0 and C0/ (C16 + C18) ratio and NGS are necessary for the identification and diagnosis of CPT1A deficiency. The c.1846G>A and c.2201T>C variants of the CPT1A gene probably underlay the disease in this child. Above finding has also enriched the spectrum of CPT1A gene variants.
Carnitine/blood* ; Carnitine O-Palmitoyltransferase/genetics* ; Child ; DNA Mutational Analysis ; Female ; Humans ; Hypoglycemia/genetics* ; Lipid Metabolism, Inborn Errors/genetics*

BACKGROUND: Abnormally activated mechanistic target of rapamycin (mTOR) pathway has been reported in several model animals with inherited metabolic myopathies (IMMs). However, the profiles of mTOR pathway in skeletal muscles from patients are still unknown. This study aimed to analyze the activity of mTOR pathway in IMMs muscles. METHODS: We collected muscle samples from 25 patients with mitochondrial myopathy (MM), lipid storage disease (LSD) or Pompe disease (PD). To evaluate the activity of mTOR pathway in muscle specimens, phosphorylation of S6 ribosomal protein (p-S6) and p70S6 kinase (p-p70S6K) were analyzed by Western blotting and immunohistochemistry. RESULTS: Western blotting results showed that p-p70S6K/p70S6K in muscles from LSD and MM was up-regulated when compared with normal controls (NC) (NC vs. LSD, U = 2.000, P = 0.024; NC vs. MM: U = 6.000, P = 0.043). Likewise, p-S6/S6 was also up-regulated in muscles from all three subgroups of IMMs (NC vs. LSD, U = 0.000, P = 0.006; NC vs. PD, U = 0.000, P = 0.006; NC vs. MM, U = 1.000, P = 0.007). Immunohistochemical study revealed that p-S6 was mainly expressed in fibers with metabolic defect. In MM muscles, most p-S6 positive fibers showed cytochrome C oxidase (COX) deficiency (U = 5.000, P = 0.001). In LSD and PD muscles, p-S6 was mainly overexpressed in fibers with intramuscular vacuoles containing lipid droplets (U = 0.000, P = 0.002) or basophilic materials (U = 0.000, P = 0.002). CONCLUSION The mTOR pathway might be activated in myofibers with various metabolic defects, which might provide evidence for mTOR inhibition therapy in human IMMs.
Adolescent ; Adult ; Aged ; Blotting, Western ; Child ; Child, Preschool ; Female ; Glycogen Storage Disease Type II ; genetics ; metabolism ; Humans ; Immunohistochemistry ; In Vitro Techniques ; Lipid Metabolism, Inborn Errors ; genetics ; metabolism ; Male ; Middle Aged ; Mitochondrial Myopathies ; genetics ; metabolism ; Muscular Diseases ; genetics ; metabolism ; Signal Transduction ; genetics ; physiology ; TOR Serine-Threonine Kinases ; metabolism ; Young Adult

OBJECTIVE: To detect potential variation in an ethnic Han Chinese family affected with late-onset lipid storage myopathy. METHODS: Next generation sequencing (NGS) was used to screen disease-related genes in the proband. Suspected mutation was validated with PCR and Sanger sequencing in two patients, their father, and 100 healthy controls. RESULTS: Heterozygous c.770A>G (p.Tyr257Cys) and c.1395dupT (p.Gly466Tryfs) mutation were detected in the two patients. Their father was found to be heterozygous for the c.770A>G (p.Tyr257Cys) mutation, while the c.1395dupT (p.Gly466Tryfs) variation was not reported previously and not found among the healthy controls. CONCLUSION Mutations of the ETFDH gene probably underlie the pathogenesis in this family. The novel c.1395dupT (p.Gly466Tryfs) has enriched the mutation spectrum of EDFDH gene.
Asian Continental Ancestry Group ; Electron-Transferring Flavoproteins ; genetics ; Heterozygote ; High-Throughput Nucleotide Sequencing ; Humans ; Iron-Sulfur Proteins ; genetics ; Lipid Metabolism, Inborn Errors ; genetics ; Muscular Dystrophies ; genetics ; Mutation ; Oxidoreductases Acting on CH-NH Group Donors ; genetics

OBJECTIVE: To explore the clinical features and variations of ACADVL gene in 9 neonates with very long chain acyl-coenzyme A dehydrogenase deficiency (VLCADD). METHODS: VLCADD was suspected based on the results of neonatal screening by tandem mass spectrometry (MS-MS), with tetradecenoylcarnitine ± tetradecenoylcarnitine/octanoylcarnitine (C14: 1 ± C14: 1/C8) as the mark indexes. Infants with positive outcome were confirmed by sequencing of the ACADVL gene. RESULTS: Among 9 VLCADD cases, one case lost during follow-up, the observed phenotypes comprised 2 with severe early-onset form, 1 with hepatic form and 5 with late-onset form. Optimal outcome was acquired for all patients except the 2 early-onset cases. In total 16 ACADVL variations were detected among the 9 infants, which included 8 novel variations (c.96-105del GCCCGGCCCT, c.541C>T, c.863T>G, c.878+1G>C, c.895A>G, c.1238T>C, c.1276G>A, and c.1505T>A) and 11 missense variations. There were 9 genotypic combinations, including 1 homozygote and 8 compound heterozygotes. Except for two patients carrying null variations, all had a good outcome. CONCLUSION VLCADD is relatively rare in southern China, for which late-onset form is common. Carriers of null variations of the ACADVL gene may have relatively poorer clinical outcome. Above results will provide valuable information for the diagnosis and management of VLCADD.
Acyl-CoA Dehydrogenase, Long-Chain ; deficiency ; genetics ; Carnitine ; China ; Humans ; Infant, Newborn ; Lipid Metabolism, Inborn Errors ; genetics ; Mitochondrial Diseases ; genetics ; Muscular Diseases ; genetics ; Neonatal Screening

OBJECTIVETo analyze the clinical and molecular features of a child with carnitine palmitoyltransferase 1A (CPT1A) deficiency.

METHODSClinical data of the child was collected. Blood acylcarnitine was determined with tandem mass spectrometry. DNA was extracted from the child and his parents. All exons and flanking regions of the CPT1A gene were analyzed by PCR and Sanger sequencing.

RESULTSAnalysis showed that the patient carried compound heterozygous mutations c.1787T>C and c.2201T>C of the CPT1A gene, which derived his father and mother, respectively. Both mutations were verified as novel through the retrieval of dbSNP, HGMD and 1000 genome databases. Bioinformatic analysis suggested that the mutations can affect protein function.

CONCLUSIONAcyl carnitine analysis has been the main method for the diagnosis of CPT1A deficiency. The c.1787T>C and c.2201T>C mutations of the CPT1A gene probably underlie the disease in this patient. Gene testing can provide important clues for genetic counseling and prenatal diagnosis.

Base Sequence ; Carnitine O-Palmitoyltransferase ; deficiency ; genetics ; Exons ; Female ; Humans ; Hypoglycemia ; enzymology ; genetics ; Infant ; Lipid Metabolism, Inborn Errors ; enzymology ; genetics ; Male ; Molecular Sequence Data ; Point Mutation ; Pregnancy