VLCAD deficiency

Three forms of this disorder occur: a severe early-onset form with CARDIOMYOPATHY and high mortality; an intermediate form with childhood onset and hypoketotic hypoglycemia and more favorable outcome; and an adult-onset form characterized by MYOPATHY; RHABDOMYOLYSIS, and MYOGLOBINURIA after exercise or fasting. Germline mutations in the ACADS gene have been identified. OMIM: 201470

Also Known As:

Acadvl; Acyl-CoA Dehydrogenase, Very Long-Chain, Deficiency of; Acyl-Coa Dehydrogenase Very Long Chain Deficiency; Pearson Marrow-Pancreas Syndrome; Pearson syndrome; Pearson's marrow-pancreas syndrome; Sideroblastic anemia with marrow cell vacuolization and exocrine pancreatic dysfunction; Very Long-Chain Acyl Coenzyme A Dehydrogenase Deficiency; Very Long-Chain Acyl-Coenzyme A Dehydrogenase Deficiency; Very long-chain acyl-CoA dehydrogenase deficiency; Vlcad-C; Vlcad-H

Networked: 421 relevant articles (6 outcomes, 27 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Late Onset Disorders
2.	VLCAD deficiency
3.	Medium chain acyl CoA dehydrogenase deficiency
4.	Kearns-Sayre Syndrome
5.	Rhabdomyolysis

Experts

1.	Spiekerkoetter, Ute: 18 articles (01/2020 - 09/2003)
2.	Tucci, Sara: 15 articles (03/2022 - 09/2010)
3.	Yamaguchi, Seiji: 14 articles (01/2022 - 02/2002)
4.	Vockley, Jerry: 10 articles (01/2022 - 08/2006)
5.	Shigematsu, Yosuke: 9 articles (11/2022 - 07/2003)
6.	Yamada, Kenji: 8 articles (01/2022 - 06/2018)
7.	Tajima, Go: 7 articles (11/2022 - 12/2008)
8.	Mohsen, Al-Walid: 7 articles (01/2022 - 06/2007)
9.	Ferdinandusse, Sacha: 7 articles (09/2021 - 07/2004)
10.	Wanders, Ronald J A: 7 articles (01/2020 - 07/2004)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to VLCAD deficiency:

1.	Long-Chain Acyl-CoA Dehydrogenase (Long-Chain-Acyl-Coenzyme A Dehydrogenase)IBA 08/01/2006 - "The development of a safe, durable, and effective VLCAD gene delivery system for use at the time of diagnosis could result in a significant improvement in the quality and duration of life for patients with VLCAD deficiency. " 01/01/2017 - "Very long-chain acyl-CoA dehydrogenase (VLCAD-) deficiency-studies on treatment effects and long-term outcomes in mouse models." 06/01/2005 - "The VLCAD-deficient mouse exhibits similar clinical and biochemical phenotypes to those observed in humans and, therefore, represents an excellent model to study VLCAD deficiency. " 10/25/2023 - "With the patient's informed consent, acyl-CoA dehydrogenase very long-chain (ACADVL) gene analysis revealed compound heterozygous mutations of c.1332G>A in exon 13 and c.1349G>A (p.R450H) in exon 14. " 11/01/2022 - "The clinical severity of very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is difficult to predict using conventional diagnostic methods. "
2.	Triglycerides (Triacylglycerol)IBA 01/01/2017 - "Treatment for VLCAD-deficiency includes avoidance of fasting and a long-chain fat-restricted and fat-modified diet in which LCFAs are fully or partially replaced by medium-chain triglycerides (MCT). " 05/01/2018 - "After VLCAD deficiency diagnosis, the subject was treated with the administration of a medium chain triglyceride formula and fluid therapy. " 11/01/2015 - "An even medium-chain triglyceride (MCT)-based diet is the mainstay of treatment in very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency (VLCADD). " 09/01/2010 - "A medium-chain-triglyceride (MCT)-based diet is mainstay of treatment in very-long-chain acyl-CoA dehydrogenase deficiency (VLCADD), a long-chain fatty acid beta-oxidation defect. " 01/01/2019 - "Patients with very long chain acyl-CoA dehydrogenase deficiency (VLCADD), a long chain fatty acid oxidation disorder, are traditionally treated with a long chain triglyceride (LCT) restricted and medium chain triglyceride (MCT) supplemented diet. "
3.	Fatty Acids (Saturated Fatty Acids)IBA 12/01/2022 - "This study illustrated that cutaneous fatty acid metabolism was altered in the early response of ionizing radiation, and fatty acid metabolism-associated ACADVL is involved in radiation-induced cell death." 01/01/2018 - "The findings of the present study indicate that the major long-chain fatty acids that accumulate in VLCAD deficiency disrupt mitochondrial bioenergetics and Ca2+ homeostasis, acting as uncouplers and metabolic inhibitors of oxidative phosphorylation, as well as inducers of MPT pore opening, in the heart at pathological relevant concentrations. " 12/01/2023 - "To define the biochemical and molecular characteristics and diagnostic outcomes of a large US cohort of VLCAD deficiency positive cases as detected by newborn screening (NBS) with MS:MS. This relatively common disorder of fatty acid oxidation is screened for in every state in America and often results in extensive testing of multiple samples to arrive at a diagnostic conclusion. " 10/25/2023 - "With the introduction of tandem mass screening in 2014, fatty acid metabolism disorders, including VLCAD deficiency, are being detected before the onset of symptoms. " 06/01/2023 - "Very long-chain acyl-CoA dehydrogenase deficiency (VLCADD) is a rare autosomal recessive disorder of fatty acid metabolism. "
4.	BezafibrateIBA 02/01/2021 - "Efficacy of bezafibrate for preventing myopathic attacks in patients with very long-chain acyl-CoA dehydrogenase deficiency." 09/15/2005 - "Bezafibrate also diminished the production of toxic long-chain acylcarnitines by 90% in cells harboring moderate VLCAD deficiency. " 12/01/2007 - "Genetic basis for correction of very-long-chain acyl-coenzyme A dehydrogenase deficiency by bezafibrate in patient fibroblasts: toward a genotype-based therapy." 12/01/2007 - "Finally, this study emphasizes the potential of bezafibrate, a widely prescribed hypolipidemic drug, for the correction of VLCAD deficiency and exemplifies the integration of molecular information in a therapeutic strategy." 01/01/2021 - "Bezafibrate activation of PPAR drives disturbances in mitochondrial redox bioenergetics and decreases the viability of cells from patients with VLCAD deficiency."
5.	Adenosine Monophosphate (AMP)IBA 11/01/2023 - "Therefore, an ACADVL-specific variant curation expert panel (VCEP) was created to facilitate the specification of the ACMG/AMP guidelines for VLCADD. " 11/01/2023 - "Specifications of the ACMG/AMP guidelines for ACADVL variant interpretation." 11/01/2023 - "Although the ACMG/AMP guidelines have helped standardize variant classification, ACADVL variant classification remains disparate due to a phenotype that can be nonspecific, the possibility of variants that produce late-onset disease, and relatively high carrier frequency, amongst other challenges. " 04/01/2022 - "miR-370 and Let-7 expression increased with acute and chronic exposure to HFD, accompanied by carnitine palmitoyltransferase 1A (Cpt1a), acyl-CoA dehydrogenase very long chain (Acadvl) and protein kinase AMP-activated Catalytic Subunit 2 (Prkaa2) downregulation, while decreased miR-122 expression was accompanied by 1-acylglycerol-3-phosphate-O-acyltransferase (Agpat) upregulation after 56 days of HFD consumption, some of them confirmed by in vitro experiments. " 01/01/2022 - ": 7,8-DHF: 7,8-dihydroxyflavone; ACACA/ACC: acetyl Coenzyme A carboxylase alpha; ACAD: acyl-Coenzyme A dehydrogenase family; ACADVL: acyl-Coenzyme A dehydrogenase, very long chain; ACOT: acyl-CoA thioesterase; CAMKK2: calcium/calmodulin-dependent protein kinase kinase 2, beta; BDNF: brain derived neurotrophic factor; BNIP3: BCL2/adenovirus E1B interacting protein 3; BNIP3L/NIX: BCL2/adenovirus E1B interacting protein 3-like; CCL2/MCP-1: chemokine (C-C motif) ligand 2; CCL5: chemokine (C-C motif) ligand 5; CNS: central nervous system; CPT1B: carnitine palmitoyltransferase 1b, muscle; Cpt2: carnitine palmitoyltransferase 2; CREB: cAMP responsive element binding protein; DNM1L/DRP1: dynamin 1-like; E2: estrogen; EHHADH: enoyl-CoenzymeA hydratase/3-hydroxyacyl CoenzymeA dehydrogenase; ESR1/ER-alpha: estrogen receptor 1 (alpha); FA: fatty acid; FAO: fatty acid oxidation; FCCP: carbonyl cyanide-4-(trifluoromethoxy)phenylhydrazone; FFA: free fatty acids; FGF21: fibroblast growth factor 21; FUNDC1: FUN14 domain containing 1; HADHA: hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit alpha; HFD: high-fat diet; iWAT: inguinal white adipose tissues; MAP1LC3A/LC3A: microtubule-associated protein 1 light chain 3 alpha; MBKO; muscle-specific bdnf knockout; IL6/IL-6: interleukin 6; MCEE: methylmalonyl CoA epimerase; MFF: mitochondrial fission factor; NTRK2/TRKB: neurotrophic tyrosine kinase, receptor, type 2; OPTN: optineurin; PA: palmitic acid; PARL: presenilin associated, rhomboid-like; PDH: pyruvate dehydrogenase; PINK1: PTEN induced putative kinase 1; PPARGC1A/PGC-1α: peroxisome proliferative activated receptor, gamma, coactivator 1 alpha; PRKAA/AMPK: protein kinase, AMP-activated, alpha 2 catalytic subunit; ROS: reactive oxygen species; TBK1: TANK-binding kinase 1; TG: triacylglycerides; TNF/TNFα: tumor necrosis factor; TOMM20: translocase of outer mitochondrial membrane 20; ULK1: unc-51 like kinase 1."
6.	EnzymesIBA 11/01/2018 - "In this study, we show the outcome of enzyme testing in lymphocytes as a confirmatory tool in newborns identified by screening, and the correlation with molecular sequencing of the ACADVL gene. " 07/15/2003 - "Although the diagnostic ratio of tetradecenoylcarnitine to dodecanoylcarnitine for very long-chain acyl CoA dehydrogenase deficiency seemed to minimize the overlapping in this study, additional measures including careful assessment of clinical data and enzyme assays may be necessary for the diagnosis in atypical cases." 08/01/1998 - "Biochemical studies indicated VLCAD deficiency caused by a stable yet inactive enzyme. " 11/21/2023 - "Independent of MCAD enzyme activity, rAAV6:MCAD increased Acadl and Acadvl in the non-diabetic heart. " 03/01/2022 - "Very long-chain acyl-CoA dehydrogenase deficiency in a Swedish cohort: Clinical symptoms, newborn screening, enzyme activity, and genetics."
7.	Carnitine (L-Carnitine)FDA LinkGeneric 08/02/2013 - "The increased levels of tetradecenoyl carnitine in patient's dried blood spot suggested a VLCAD deficiency, which was confirmed by molecular study. " 01/01/2019 - "VLCAD deficiency (screened by measuring elevated levels of C14:1-carnitine in blood spots) was more frequent in Utah than the national average (1:27,617 versus 1:63,481) in the first ten years of screening. " 06/01/2018 - "l-Carnitine supplementation for patients with VLCAD deficiency is controversial. " 01/01/2016 - "The natural history of elevated tetradecenoyl-L-carnitine detected by newborn screening in New Zealand: implications for very long chain acyl-CoA dehydrogenase deficiency screening and treatment." 08/01/2009 - "l-Carnitine was supplemented in about half of the patients, but in none of the patients with VLCAD deficiency identified by newborn screening. "
8.	DNA (Deoxyribonucleic Acid)IBA 01/01/2019 - "Twenty-six patients had a confirmed diagnosis of VLCAD deficiency using DNA testing or functional studies. " 05/01/2013 - "ACADVL genomic DNA sequencing data were available for twelve of them. " 08/01/2009 - "The sequenced clone analysis of a complimentary DNA fragment revealed a compound heterozygote mutation of exon 9 (A790G) and exon 10 (997 ins T), which is a novel mutation of a myopathic-type very-long-chain acyl-CoA dehydrogenase deficiency. " 05/01/1999 - "DNA-based prenatal diagnosis for very-long-chain acyl-CoA dehydrogenase deficiency." 01/22/2001 - "We report on a seven-year-old Japanese boy with Pearson syndrome, which is characterized by refractory sideroblastic anemia with vacuolization of marrow precursors and dysfunction of the exocrine pancreas, and caused by mitochondrial (mt) DNA deletions and duplications. "
9.	Mitochondrial DNA (mtDNA)IBA 01/01/2022 - "Development and characterization of cell models harbouring mtDNA deletions for in vitro study of Pearson syndrome." 09/01/2011 - "We report the case of a 14 month-old girl evaluated by a multicentric study, with clinic and molecular diagnosis of Pearson syndrome, with the 4,977-base pair common deletion of mitochondrial DNA. " 12/01/2023 - "The First Reported Case of a Child with Two Different Rare Metabolic Disorders: Very Long-Chain Acyl-CoA Dehydrogenase Deficiency and Encephalomyopathic Mitochondrial DNA Depletion Syndrome 13." 08/01/2023 - "The Pearson syndrome (PS) patient harbored nuclear mutations in the POLG and SSBP1 genes, which could induce systemic large-scale mitochondrial genome (mtDNA) deletion. " 01/01/2022 - "Pearson syndrome is a rare multisystem disease caused by single large-scale mitochondrial DNA deletions (SLSMDs). "
10.	Acyl-CoA Dehydrogenase (Medium-Chain Acyl-Coenzyme A Dehydrogenase)IBA 04/17/2015 - "Very long acyl-CoA dehydrogenase (VLCAD) deficiency is a genetic pediatric disorder presenting with a spectrum of phenotypes that remains for the most part untreatable. " 12/16/2022 - "Our previous study on the liver transcriptome of Holstein cows found that acyl-CoA dehydrogenase (ACADVL) and interferon regulatory factor 6 (IRF6) are differentially expressed between dry and peak lactation periods, as well as that they are involved in lipid metabolism and the proliferation and differentiation of mammary epithelial cells. " 10/25/2023 - "Enzyme activity measurement in the patient's peripheral blood lymphocytes confirmed the diagnosis of VLCAD deficiency, with low palmitoyl-CoA dehydrogenase levels (6.5% of normal control value). " 10/01/2021 - "On d -11 relative to LPS, differences between the mRNA abundance in CON and CAR were limited to acyl-CoA dehydrogenase (ACAD) very-long-chain (ACADVL) with greater mRNA abundance in the CAR than in the CON group. " 10/01/2016 - "In a GeneFishing experiment using human preeclamptic placenta, expression of acyl-coenzyme A dehydrogenase very long chain (ACADVL), which is involved in fatty acid β-oxidation (FAO), was detected. "

Therapies and Procedures

1.	Therapeutics 03/01/2009 - "While dietary therapy for VLCAD deficiency has proven beneficial in preventing some symptoms, a risk of metabolic catastrophic decompensation remains throughout life during times of increased energy demand. " 01/01/2022 - "Some differences observed among models may depend on their metabolic profile; therefore, we consider that these three models are useful for the in vitro study of Pearson syndrome, as well as for testing new specific therapies. " 01/01/2022 - "Prognosis is poor and treatment is supportive, thus the development of new models for the study of Pearson syndrome and new therapy strategies is essential. " 08/01/2006 - "Through the expansion of newborn screening programs an increasing number of individuals with VLCAD deficiency are being identified prior to the onset of symptoms allowing early initiation of therapy. " 08/08/2023 - "Since dietary treatment is the only therapy available for treating VLCAD deficiency and it is more useful the earlier it is started, prompt diagnosis is essential in order to minimize muscle damage and slow the disease progression."
2.	Anesthesia 09/16/2020 - "Anesthesia management in a patient with very long-chain acyl-Coenzyme A dehydrogenase deficiency." 01/01/2018 - "Volatile anesthesia for a pediatric patient with very long-chain acyl-coenzyme A dehydrogenase deficiency: A case report." 01/01/2017 - "Surgery and anesthesia pose a threat to patients with very long-chain acyl-CoA dehydrogenase deficiency (VLCADD), because prolonged fasting, stress, and pain are known risk factors for the induction of metabolic derangement. " 09/01/2009 - "Early recovery from anesthesia and extubation in an infant with very long chain acyl-CoA dehydrogenase deficiency using midazolam, mivacurium, and high dose remifentanil."
3.	Cell- and Tissue-Based Therapy (Cell Therapy) 08/01/2023 - "Selection of iPSCs without mtDNA deletion for autologous cell therapy in a patient with Pearson syndrome." 09/15/2005 - "Cell therapy of VLCAD deficiency was related to drug-induced increases in VLCAD mRNA (+44 to +150%; P<0.001), protein (1.5-2-fold) and residual enzyme activity (up to 7.7-fold) in patient cells. "
4.	Intravenous Administration 01/01/2023 - "Intravenous administration of LNP-VLCAD to Acadvl-/- mice produced a significant amount of VLCAD protein in liver, which declined over a week. "
5.	Resistance Training 01/01/2019 - "Combined HIIT and Resistance Training in Very Long-Chain Acyl-CoA Dehydrogenase Deficiency: A Case Report."