ArticleOrphanet journal of rare diseases2014
Clinical and genetical heterogeneity of late-onset multiple acyl-coenzyme A dehydrogenase deficiency.
Article in Orphanet journal of rare diseases, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers, 3 of them syntheses that pooled it.
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Who cites it
100 citing papers in PubMed, 3 syntheses or guidelines pooled it, 204 citations in OpenAlex.
- Effectiveness of Riboflavin in Inherited Metabolic Diseases: A Systematic Review.Journal of inherited metabolic disease · 2026Pooled it
- The difference of variation types between late-onset multiple acyl-CoA dehydrogenase deficiency patients carrying biallelic and single heterozygous variations in ETFDH: a systematic review and meta-analysis.Orphanet journal of rare diseases · 2025Pooled it
- The male-to-female ratio in late-onset multiple acyl-CoA dehydrogenase deficiency: a systematic review and meta-analysis.Orphanet journal of rare diseases · 2024Pooled it
- Trial
- Genotype-environment interaction drives the onset of riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency in carriers of single heterozygous ETFDH variants.Cell communication and signaling : CCS · 2026Article
- Splicing defect and functional characterization of the ETFDH c.1049G > A VUS underlying transient MADD: an iPSC and minigene study.Orphanet journal of rare diseases · 2026Article
- Fully Automated Serum LC-MS/MS Platform and Pediatric Reference Intervals for Organic Acids, Amino Acids, and Acylcarnitines in Children (Ages 0-6 Years): Toward Quantitative Diagnosis of Inborn Errors of Metabolism.Diagnostics (Basel, Switzerland) · 2026Article
- Acquired Multiple Acyl-Coenzyme A Dehydrogenase Deficiency Associated With Sertraline in Sweden-A Nationwide Population-Based Study.European journal of neurology · 2026Article
- Spinal Cord Involvement in Patients with Adult-Onset Multiple Acyl-CoA Dehydrogenase Deficiency.Neuromolecular medicine · 2026Article
- Glutaric acidemia type 2 presenting as a surgical acute abdomen: a case of unnecessary exploratory laparotomy in an adult.Archive of clinical cases · 2026Article
- A Case of Suspected Multiple Acyl-CoA Dehydrogenase Deficiency-Induced Encephalopathy.Case reports in critical care · 2026Article
- Late-Onset Multiple Acyl-CoA Dehydrogenase Deficiency (MADD): Clinical Features, Diagnostic Challenges, and the Role of Oxidative Stress in Pathophysiology.Antioxidants (Basel, Switzerland) · 2025Article
- First report of neonatal-onset glutaric aciduria type II in the Iranian population caused by a novel deleterious ETFA variant.Orphanet journal of rare diseases · 2025Article
- PET/CT and exome sequencing in late onset multiple acyl-CoA dehydrogenase deficiency: a case series and literature review.BMC medical genomics · 2025Review
- Late-Onset Multiple Acyl-CoA Dehydrogenase Deficiency (MADD): A Case Report With a Complex Biochemical Profile.JIMD reports · 2025Article
- Therapies for Mitochondrial Disease: Past, Present, and Future.Journal of inherited metabolic disease · 2025Review
- The Establishment of Expanded Newborn Screening in Rural Areas of a Developing Country: A Model from Health Regions 7 and 8 in Thailand.International journal of neonatal screening · 2025Article
- Identification of ETFDH gene c. 487 + 2 T > A pathogenic variant and mechanisms for polycystic kidney in neonatal onset MADD.Orphanet journal of rare diseases · 2025Article
- Analysis of human urinary extracellular vesicles reveals disordered renal metabolism in myotonic dystrophy type 1.Nature communications · 2025Article
- 2-[JIMD reports · 2025Article
40 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
1 author at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMultiple acyl-CoA dehydrogenase deficiency (MADD) is an autosomal recessive disorder caused by deficiency of electron transfer flavoprotein or electron transfer flavoprotein dehydrogenase. The clinical picture of late-onset forms is highly variable with symptoms ranging from acute metabolic decompensations to chronic, mainly muscular problems or even asymptomatic cases.
methodsAll 350 cases of late-onset MADD reported in the literature to date have been analyzed and evaluated with respect to age at presentation, diagnostic delay, biochemical features and diagnostic parameters as well as response to treatment.
resultsMean age at onset was 19.2 years. The mean delay between onset of symptoms and diagnosis was 3.9 years. Chronic muscular symptoms were more than twice as common as acute metabolic decompensations (85% versus 33% of patients, respectively). 20% had both acute and chronic symptoms. 5% of patients had died at a mean age of 5.8 years, while 3% of patients have remained asymptomatic until a maximum age of 14 years. Diagnosis may be difficult as a relevant number of patients do not display typical biochemical patterns of urine organic acids and blood acylcarnitines during times of wellbeing. The vast majority of patients carry mutations in the ETFDH gene (93%), while mutations in the ETFA (5%) and ETFB (2%) genes are the exceptions. Almost all patients with late-onset MADD (98%) are clearly responsive to riboflavin.
conclusionsLate-onset MADD is probably an underdiagnosed disease and should be considered in all patients with acute or chronic muscular symptoms or acute metabolic decompensation with hypoglycemia, acidosis, encephalopathy and hepatopathy. This may not only prevent patients from invasive diagnostic procedures such as muscle biopsies, but also help to avoid fatal metabolic decompensations.
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