RARE DISEASE
Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency
Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency
Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency
Synonyms: LCHAD deficiency, LCHADD, Long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency
Synonyms: LCHAD deficiency, LCHADD, Long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency
Synonyms: LCHAD deficiency, LCHADD, Long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency
Drug discovery
3
drugs
With orphan designations
Overview
Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency is a rare autosomal recessive disorder of mitochondrial fatty acid oxidation caused by HADHA gene mutations, impairing long-chain fatty acid breakdown. It presents in infancy/childhood with hypoketotic hypoglycemia, cardiomyopathy, hepatopathy, retinopathy, and peripheral neuropathy. Metabolic crises, triggered by fasting or illness, risk sudden death. Diagnosis involves newborn screening (elevated hydroxyacylcarnitines) and genetic confirmation. Management prioritizes fasting avoidance, medium-chain triglyceride (MCT) supplementation, and emergency glucose during catabolic states [1][3][6][15][17].
Categories: rare cardiac diseases, rare endocrine diseases, rare genetic diseases, rare inborn errors of metabolism, rare neurological diseases, rare ophthalmic disorders, rare transplant-related disorders
Research Papers
104 drug discovery papers about Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency, with 1 first-in-class and 1 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
104 drug discovery papers about Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency, with 1 first-in-class and 1 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-04-28 | Bezafibrate-MCT Oil Combination Therapy for Enhanced Alternative Energy Metabolism
Bezafibrate activates PPARα to upregulate medium-chain acyl-CoA dehydrogenase (MCAD) and short-chain acyl-CoA dehydrogenase (SCAD) expression. Combined with medium-chain triglyceride oil, this bypasses the LCHAD deficiency by providing readily oxidizable medium-chain fatty acids while enhancing the enzymatic capacity for their metabolism through peroxisome proliferator response elements.
2026-04-28 | Coenzyme Q10 and Idebenone Combination for Mitochondrial Electron Transport Chain Enhancement
Coenzyme Q10 enhances electron transport chain efficiency at Complex III, while idebenone acts as an alternative electron acceptor bypassing Complex I dysfunction secondary to LCHAD deficiency. This combination improves ATP synthesis efficiency and reduces accumulation of toxic long-chain 3-hydroxyacyl-CoA intermediates through enhanced mitochondrial respiratory capacity.
2026-04-28 | Ashwagandha Withanolide A for Mitochondrial Stress Response in LCHAD Deficiency
Withanolide A activates the mitochondrial unfolded protein response (UPRmt) through ATF5 and CHOP transcription factors, enhancing mitochondrial protein quality control. It stabilizes remaining LCHAD enzyme through heat shock protein 60 (HSP60) upregulation and reduces oxidative stress via Nrf2-mediated antioxidant response.
2026-03-11 | Single-nuclei transcriptomic profiling of human myocardium in long chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency
Single-nuclei transcriptomic profiling of human myocardium in long chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency Hanna J. Tadros MBBCh1, Diwakar Turaga MD, PhD2,3, Yi Zhao PhD6, Chang-Ru Tsai, PhD9, Lalita Wadhwa PhD4, Debra L. Kearney MD7, Iki Adachi MD4,5, Xiao Li PhD6,8, James F. Martin MD, PhD6,9,10* 1. Department of Pediatrics, Section of Pediatric Cardiology, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA. 2. Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA 3. Division of Critical Care Medicine, Texas Children's Hospital, Houston TX, USA 4. Department of Surgery, Baylor College of Medicine, Houston, TX, USA 5. Division of Congenital Heart Surgery, Texas Children's Hospital, Houston, TX, USA 6. The Texas Heart Institute at Baylor College of Medicine, Houston, TX, USA 7. Department of Pathology, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA 8. Department of Medicine, Baylor College of Medicine, Houston, TX, USA 9. Department of Integrative Physiology, Baylor College of Medicine, Houston, TX, USA 10. Center for Organ Repair and Renewal, Baylor College of Medicine, Houston, TX, USA *Corresponding author. Email: jfmartin@bcm.edu
2026-02-01 | Acute Fatty Liver of Pregnancy and Fetal Fatty Acid Oxidation Disorders: A Systematic Review
OBJECTIVE: To evaluate the association between maternal acute fatty liver of pregnancy (AFLP) and fetal fatty acid oxidation (FAO) disorders and to define the clinical and genetic characteristics of mothers with AFLP and their fetuses affected by FAO disorders, we performed a systematic literature review of all reported cases of AFLP that underwent genetic testing for FAO disorders. DATA SOURCES: We searched PubMed, Ovid MEDLINE, Cochrane Library, CINAHL (EBSCO), Scopus, and ClinicalTrials.gov. Terms included were related to AFLP and FAO testing. METHODS OF STUDY SELECTION: We conducted a systematic literature review from inception through May 18, 2025, to evaluate the relationship between AFLP and fetal FAO disorders. Studies were eligible for inclusion if they evaluated the relationship between AFLP and fetal FAO disorders and provided both detailed pregnancy characteristics for AFLP and the workup of maternal and/or fetal FAO disorder. TABULATION, INTEGRATION, AND RESULTS: Twenty-seven studies with 77 AFLP cases that underwent genetic or biochemical testing for maternal or fetal FAO disorders were included. Of these 77 pregnancies, 27 (35.1%) were associated with confirmed fetal FAO disorders. The 27 neonates with FAO disorders included 22 fetuses (81.5%) with LCHAD deficiency, three (11.1%) with medium-chain acyl-CoA dehydrogenase deficiency, one (3.7%) with short-chain acyl-CoA dehydrogenase deficiency, and one (3.7%) with carnitine palmitoyl transferase-I deficiency. Stillbirth and infant mortality was reported in 14 of 22 cases (63.6%) with LCHAD deficiency, and there were no recorded fetal or neonatal deaths with other FAO disorders or those with negative genetic testing. One maternal death was reported in a pregnancy with negative genetic testing for FAO disorders and one patient in a coma at the time of publication with an LCHAD-deficient pregnancy. Presentation of AFLP with gastrointestinal manifestations occurred in 87.8% of patients. CONCLUSION: Acute fatty liver of pregnancy is associated with fetal FAO disorders in about a third of cases, with the most common FAO disorder being LCHAD deficiency. Both AFLP and LCHAD deficiency are associated with high morbidity and mortality in mothers and neonates. Evaluation for fetal and maternal LCHAD deficiency should be part of the diagnostic evaluation in AFLP. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42021247166.
2026-04-28 | Bezafibrate-MCT Oil Combination Therapy for Enhanced Alternative Energy Metabolism
Bezafibrate activates PPARα to upregulate medium-chain acyl-CoA dehydrogenase (MCAD) and short-chain acyl-CoA dehydrogenase (SCAD) expression. Combined with medium-chain triglyceride oil, this bypasses the LCHAD deficiency by providing readily oxidizable medium-chain fatty acids while enhancing the enzymatic capacity for their metabolism through peroxisome proliferator response elements.
2026-04-28 | Coenzyme Q10 and Idebenone Combination for Mitochondrial Electron Transport Chain Enhancement
Coenzyme Q10 enhances electron transport chain efficiency at Complex III, while idebenone acts as an alternative electron acceptor bypassing Complex I dysfunction secondary to LCHAD deficiency. This combination improves ATP synthesis efficiency and reduces accumulation of toxic long-chain 3-hydroxyacyl-CoA intermediates through enhanced mitochondrial respiratory capacity.
2026-04-28 | Ashwagandha Withanolide A for Mitochondrial Stress Response in LCHAD Deficiency
Withanolide A activates the mitochondrial unfolded protein response (UPRmt) through ATF5 and CHOP transcription factors, enhancing mitochondrial protein quality control. It stabilizes remaining LCHAD enzyme through heat shock protein 60 (HSP60) upregulation and reduces oxidative stress via Nrf2-mediated antioxidant response.
2026-03-11 | Single-nuclei transcriptomic profiling of human myocardium in long chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency
Single-nuclei transcriptomic profiling of human myocardium in long chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency Hanna J. Tadros MBBCh1, Diwakar Turaga MD, PhD2,3, Yi Zhao PhD6, Chang-Ru Tsai, PhD9, Lalita Wadhwa PhD4, Debra L. Kearney MD7, Iki Adachi MD4,5, Xiao Li PhD6,8, James F. Martin MD, PhD6,9,10* 1. Department of Pediatrics, Section of Pediatric Cardiology, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA. 2. Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA 3. Division of Critical Care Medicine, Texas Children's Hospital, Houston TX, USA 4. Department of Surgery, Baylor College of Medicine, Houston, TX, USA 5. Division of Congenital Heart Surgery, Texas Children's Hospital, Houston, TX, USA 6. The Texas Heart Institute at Baylor College of Medicine, Houston, TX, USA 7. Department of Pathology, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA 8. Department of Medicine, Baylor College of Medicine, Houston, TX, USA 9. Department of Integrative Physiology, Baylor College of Medicine, Houston, TX, USA 10. Center for Organ Repair and Renewal, Baylor College of Medicine, Houston, TX, USA *Corresponding author. Email: jfmartin@bcm.edu
2026-02-01 | Acute Fatty Liver of Pregnancy and Fetal Fatty Acid Oxidation Disorders: A Systematic Review
OBJECTIVE: To evaluate the association between maternal acute fatty liver of pregnancy (AFLP) and fetal fatty acid oxidation (FAO) disorders and to define the clinical and genetic characteristics of mothers with AFLP and their fetuses affected by FAO disorders, we performed a systematic literature review of all reported cases of AFLP that underwent genetic testing for FAO disorders. DATA SOURCES: We searched PubMed, Ovid MEDLINE, Cochrane Library, CINAHL (EBSCO), Scopus, and ClinicalTrials.gov. Terms included were related to AFLP and FAO testing. METHODS OF STUDY SELECTION: We conducted a systematic literature review from inception through May 18, 2025, to evaluate the relationship between AFLP and fetal FAO disorders. Studies were eligible for inclusion if they evaluated the relationship between AFLP and fetal FAO disorders and provided both detailed pregnancy characteristics for AFLP and the workup of maternal and/or fetal FAO disorder. TABULATION, INTEGRATION, AND RESULTS: Twenty-seven studies with 77 AFLP cases that underwent genetic or biochemical testing for maternal or fetal FAO disorders were included. Of these 77 pregnancies, 27 (35.1%) were associated with confirmed fetal FAO disorders. The 27 neonates with FAO disorders included 22 fetuses (81.5%) with LCHAD deficiency, three (11.1%) with medium-chain acyl-CoA dehydrogenase deficiency, one (3.7%) with short-chain acyl-CoA dehydrogenase deficiency, and one (3.7%) with carnitine palmitoyl transferase-I deficiency. Stillbirth and infant mortality was reported in 14 of 22 cases (63.6%) with LCHAD deficiency, and there were no recorded fetal or neonatal deaths with other FAO disorders or those with negative genetic testing. One maternal death was reported in a pregnancy with negative genetic testing for FAO disorders and one patient in a coma at the time of publication with an LCHAD-deficient pregnancy. Presentation of AFLP with gastrointestinal manifestations occurred in 87.8% of patients. CONCLUSION: Acute fatty liver of pregnancy is associated with fetal FAO disorders in about a third of cases, with the most common FAO disorder being LCHAD deficiency. Both AFLP and LCHAD deficiency are associated with high morbidity and mortality in mothers and neonates. Evaluation for fetal and maternal LCHAD deficiency should be part of the diagnostic evaluation in AFLP. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42021247166.
Access all drug discovery papers and probability of success in trials forecasts:
Access all drug discovery papers and probability of success in trials forecasts:
Drug Discovery Landscape
3 orphan drug designations for Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency.
3 orphan drug designations for Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Mavodelpar sodium | small molecules | EMA | 2020-08-21 | — | Scendea (NL) B.V. |
Triheptanoin | small molecules | EMA | 2015-07-28 | — | Ultragenyx Netherlands B.V. |
Triheptanoin [Triheptanoin] | small molecules | EMA | 2012-12-06 | — | B. Braun Melsungen AG |
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