RARE DISEASE
Medium chain acyl-CoA dehydrogenase deficiency
Medium chain acyl-CoA dehydrogenase deficiency
Medium chain acyl-CoA dehydrogenase deficiency
Synonyms: ACADM deficiency, Carnitine deficiency secondary to medium-chain acyl-CoA dehydrogenase deficiency, MCAD deficiency, MCADD, Medium chain acyl-coenzyme A dehydrogenase deficiency
Synonyms: ACADM deficiency, Carnitine deficiency secondary to medium-chain acyl-CoA dehydrogenase deficiency, MCAD deficiency, MCADD, Medium chain acyl-coenzyme A dehydrogenase deficiency
Synonyms: ACADM deficiency, Carnitine deficiency secondary to medium-chain acyl-CoA dehydrogenase deficiency, MCAD deficiency, MCADD, Medium chain acyl-coenzyme A dehydrogenase deficiency
Drug discovery
1
drug
With orphan designation
Overview
Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is an autosomal recessive disorder impairing mitochondrial fatty acid β-oxidation, leading to hypoketotic hypoglycemia, lethargy, hepatomegaly, and metabolic crises during fasting or illness. Caused by ACADM gene mutations, it is included in newborn screening. Early diagnosis allows preventive strategies, including avoidance of fasting and emergency glucose management, significantly reducing mortality and morbidity risks. Untreated, it can cause seizures, coma, or sudden death [1][2][9].
Categories: rare genetic diseases, rare inborn errors of metabolism
Research Papers
102 drug discovery papers about Medium chain acyl-CoA dehydrogenase deficiency, with 1 first-in-class and 2 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
102 drug discovery papers about Medium chain acyl-CoA dehydrogenase deficiency, with 1 first-in-class and 2 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-08-17 | [Screening and genetic variation analysis of fatty acid oxidation disorder in neonates in Qingdao City].
To investigate the incidence, genetic mutation characteristics, and prognosis of fatty acid oxidation disorder (FAOD) in neonates in Qingdao. Clinical data of neonates diagnosed with FAOD from 2014 to 2023 at the Qingdao Neonatal Disease Screening Center were collected and analyzed to determine the incidence, genotype, and prognosis. Among 562 225 neonates screened, 42 were diagnosed with FAOD across six types, yielding an overall incidence of 1/13 386. Primary carnitine deficiency was the most common (20 cases, 48%), with one case showing growth retardation during follow-up. Medium-chain acyl-CoA dehydrogenase deficiency was identified in 6 cases, all of whom demonstrated normal development during follow-up. Short-chain acyl-CoA dehydrogenase deficiency was diagnosed in 5 cases, with one case exhibiting skin erythema, papules, scaling, and dryness during follow-up. Very-long-chain acyl-CoA dehydrogenase deficiency was diagnosed in 5 cases; during follow-up, one patient died and another experienced recurrent rhabdomyolysis. Short/branched-chain acyl-CoA dehydrogenase deficiency was found in 4 cases, with one case showing language regression during follow-up. Multiple acyl-CoA dehydrogenase deficiency was detected in 2 cases; during follow-up, one patient died and one exhibited delayed motor development. Genetic testing performed on 37 of the 42 patients with FAOD identified a hotspot mutation, c.1400C>G, in the SLC22A5 gene among those with primary carnitine deficiency, whereas no predominant hotspot mutations were detected in other FAOD subtypes. In Qingdao, primary carnitine deficiency is the most prevalent subtypes of FAOD in neonates, characterized by the hotspot mutation c.1400C>G in the SLC22A5 gene. Except for very-long-chain acyl-CoA dehydrogenase deficiency and multiple acyl-CoA dehydrogenase deficiency, most children with other FAOD subtypes have a favorable prognosis.
2026-08-11 | Medium Chain Acyl-CoA Dehydrogenase Deficiency; an Unexpected Cause of Neonatal Ketoacidosis.
Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) classically presents with hypoketotic hypoglycaemia; however, this presentation is now rare following the introduction of newborn screening. While children with MCADD may produce some ketones, severe ketoacidosis has not been previously described. Here we report two patients with MCADD presenting with severe ketoacidosis in the neonatal period prior to results of newborn screening. Patient 1 presented on Day 5 with hypoglycaemia, profound ketoacidosis and circulatory shock, and developed refractory ventricular tachycardia requiring extra-corporeal membrane oxygenation. Patient 2 presented on Day 4 with severe ketoacidosis, but only borderline hypoglycaemia. The diagnosis of MCADD was rapidly confirmed in both by analysis of acylcarnitines and urine organic acids, with subsequent genetic confirmation of ACADM mutations. We conclude that MCADD should be included in the differential diagnosis of neonatal ketoacidosis, with or without hypoglycaemia.
2026-04-28 | Gymnema sylvestre Extract for Alternative Glucose Metabolism Pathway Activation
Gymnemic acids in Gymnema sylvestre activate FOXO1-mediated gluconeogenesis through G6PC and PCK1 upregulation while enhancing glycogen synthesis via GSK3β inhibition, providing glucose-based energy production to compensate for impaired fatty acid β-oxidation in MCADD patients
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 | Bezafibrate-Riboflavin Combination Therapy for MCADD Metabolic Rescue
Bezafibrate acts as a PPAR-α agonist upregulating ACADM gene expression and residual enzyme activity, while riboflavin (vitamin B2) stabilizes the FAD cofactor binding domain of mutant ACADM proteins, preventing protein misfolding and enhancing catalytic efficiency
2026-08-17 | [Screening and genetic variation analysis of fatty acid oxidation disorder in neonates in Qingdao City].
To investigate the incidence, genetic mutation characteristics, and prognosis of fatty acid oxidation disorder (FAOD) in neonates in Qingdao. Clinical data of neonates diagnosed with FAOD from 2014 to 2023 at the Qingdao Neonatal Disease Screening Center were collected and analyzed to determine the incidence, genotype, and prognosis. Among 562 225 neonates screened, 42 were diagnosed with FAOD across six types, yielding an overall incidence of 1/13 386. Primary carnitine deficiency was the most common (20 cases, 48%), with one case showing growth retardation during follow-up. Medium-chain acyl-CoA dehydrogenase deficiency was identified in 6 cases, all of whom demonstrated normal development during follow-up. Short-chain acyl-CoA dehydrogenase deficiency was diagnosed in 5 cases, with one case exhibiting skin erythema, papules, scaling, and dryness during follow-up. Very-long-chain acyl-CoA dehydrogenase deficiency was diagnosed in 5 cases; during follow-up, one patient died and another experienced recurrent rhabdomyolysis. Short/branched-chain acyl-CoA dehydrogenase deficiency was found in 4 cases, with one case showing language regression during follow-up. Multiple acyl-CoA dehydrogenase deficiency was detected in 2 cases; during follow-up, one patient died and one exhibited delayed motor development. Genetic testing performed on 37 of the 42 patients with FAOD identified a hotspot mutation, c.1400C>G, in the SLC22A5 gene among those with primary carnitine deficiency, whereas no predominant hotspot mutations were detected in other FAOD subtypes. In Qingdao, primary carnitine deficiency is the most prevalent subtypes of FAOD in neonates, characterized by the hotspot mutation c.1400C>G in the SLC22A5 gene. Except for very-long-chain acyl-CoA dehydrogenase deficiency and multiple acyl-CoA dehydrogenase deficiency, most children with other FAOD subtypes have a favorable prognosis.
2026-08-11 | Medium Chain Acyl-CoA Dehydrogenase Deficiency; an Unexpected Cause of Neonatal Ketoacidosis.
Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) classically presents with hypoketotic hypoglycaemia; however, this presentation is now rare following the introduction of newborn screening. While children with MCADD may produce some ketones, severe ketoacidosis has not been previously described. Here we report two patients with MCADD presenting with severe ketoacidosis in the neonatal period prior to results of newborn screening. Patient 1 presented on Day 5 with hypoglycaemia, profound ketoacidosis and circulatory shock, and developed refractory ventricular tachycardia requiring extra-corporeal membrane oxygenation. Patient 2 presented on Day 4 with severe ketoacidosis, but only borderline hypoglycaemia. The diagnosis of MCADD was rapidly confirmed in both by analysis of acylcarnitines and urine organic acids, with subsequent genetic confirmation of ACADM mutations. We conclude that MCADD should be included in the differential diagnosis of neonatal ketoacidosis, with or without hypoglycaemia.
2026-04-28 | Gymnema sylvestre Extract for Alternative Glucose Metabolism Pathway Activation
Gymnemic acids in Gymnema sylvestre activate FOXO1-mediated gluconeogenesis through G6PC and PCK1 upregulation while enhancing glycogen synthesis via GSK3β inhibition, providing glucose-based energy production to compensate for impaired fatty acid β-oxidation in MCADD patients
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 | Bezafibrate-Riboflavin Combination Therapy for MCADD Metabolic Rescue
Bezafibrate acts as a PPAR-α agonist upregulating ACADM gene expression and residual enzyme activity, while riboflavin (vitamin B2) stabilizes the FAD cofactor binding domain of mutant ACADM proteins, preventing protein misfolding and enhancing catalytic efficiency
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
1 orphan drug designation for Medium chain acyl-CoA dehydrogenase deficiency.
1 orphan drug designation for Medium chain acyl-CoA dehydrogenase deficiency.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Riboflavin | small molecules | EMA | 2023-11-08 | — | iniuva GmbH |
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