A systematic review of late-onset and very-late-onset multiple acyl-coenzyme A dehydrogenase deficiency: Cohort analysis and patient report from Taiwan

Kuo, Yih-Chih; Hsueh, Hsueh‐Wen; Hsueh, Sung-Ju; Lee, Ni‐Chung; Hsieh, Ming‐Ju; Chao, Chi‐Chao; Chien, Yin‐Hsiu; Huang, Pei‐Hsin; Yang, Chih‐Chao

doi:10.1016/j.nmd.2021.01.006

Cited by 8 publications

(9 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In a systematic review of PubMed, MEDLINE, and Embase databases, Kuo et al identified four cases of VLO-MADD none of whom had homozygous gene variants (as was the case in our patient), but homozygous variants were detected in 12/18 (66.6%) of patients with LO-MADD patients previously reported in Taiwan ( p = 0.014) despite no differences in clinical symptoms between VLO- and LO-MADD. 4 Since this report describes MADD in a 64-year-old with heterozygous sequence variants in the ETFDH gene, it adds to the limited evidence base that age of onset of type III MADD is correlated with the patient genotype. This poses the question whether or not type III MADD should be further subdivided by genotype into those with heterozygous and those with homozygous gene variants rather than seemingly arbitrarily by age of onset as LO-MADD and VLO-MADD currently are.…”

Section: Discussionmentioning

confidence: 89%

“…This poses the question whether or not type III MADD should be further subdivided by genotype into those with heterozygous and those with homozygous gene variants rather than seemingly arbitrarily by age of onset as LO-MADD and VLO-MADD currently are. 4…”

Section: Discussionmentioning

confidence: 99%

“…Those presenting at ages >60 years can be defined as very late onset MADD (VLO-MADD) compared to those presenting at ages <60 years as late onset MADD (LO-MADD). 4 This case report describes an unusual presentation of type III MADD in a 64-year-old female with the presenting features of dyspnoea and hyperlactatemia on a background of myalgia.…”

Section: Introductionmentioning

confidence: 92%

See 2 more Smart Citations

An unusual presentation of type III late onset multiple-acyl-CoA dehydrogenase deficiency leading to a review of its classification system

Eskell

Khan

2022

Journal of the Royal College of Physicians of Edinburgh

View full text Add to dashboard Cite

Multiple-acyl-CoA dehydrogenase deficiency (MADD) is a rare autosomal recessive disorder which can be split into three types. Type III MADD is associated with acute or subacute proximal muscle weakness and other variable non-specific features making it a challenging diagnosis for the clinician. This case report describes MADD in a 64 year-old lady, thought to be one of the latest first presentations of the disease. Unusually for this condition, the initial presentation was with dyspnoea. Furthermore, since this case provides further evidence that gene variants can predict age of onset, we advocate for further subclassification of type III MADD into late onset MADD (LO-MADD) when homozygous gene variants are present and very LO-MADD when heterozygous gene variants are found.

show abstract

Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 92%

See 1 more Smart Citation

An unusual presentation of type III late onset multiple-acyl-CoA dehydrogenase deficiency leading to a review of its classification system

Eskell

Khan

2022

Journal of the Royal College of Physicians of Edinburgh

View full text Add to dashboard Cite

show abstract

“…Acyl-CoA dehydrogenase deficiency is an inherited disorder of mitochondrial fatty acid beta- oxidation, characterised by symptoms of hypoglycaemia, muscle weakness and fatigue, typically manifesting in infancy or early childhood [ 101 ]. However, it has recently become apparent that there is a late onset form of acyl-CoA dehydrogenase deficiency, in which patients first develop symptoms at a more advanced age (>60 years) [ 102 ]. Multiple acyl-CoA dehydrogenase deficiency results from a defect of electron transport from FAD-containing CoA dehydrogenases to CoQ10 in the mitochondrial electron transport chain; this in turn is due to mutations in one of the three genes, two of which encode the alpha- and beta-subunits of the electron transfer flavoprotein ( ETFA , OMIM: 608053; ETFB OMIM: 130410), while the third encodes ETF ubiquinone oxidoreductase ( ETFDH OMIM 231675).…”

Section: Late Onset Acyl-coa Dehydrogenase Deficiencymentioning

confidence: 99%

Coenzyme Q10: Role in Less Common Age-Related Disorders

Mantle

Hargreaves

2022

Antioxidants

View full text Add to dashboard Cite

In this article we have reviewed the potential role of coenzyme Q10 (CoQ10) in the pathogenesis and treatment of a number of less common age-related disorders, for many of which effective therapies are not currently available. For most of these disorders, mitochondrial dysfunction, oxidative stress and inflammation have been implicated in the disease process, providing a rationale for the potential therapeutic use of CoQ10, because of its key roles in mitochondrial function, as an antioxidant, and as an anti-inflammatory agent. Disorders reviewed in the article include multi system atrophy, progressive supranuclear palsy, sporadic adult onset ataxia, and pulmonary fibrosis, together with late onset versions of Huntington’s disease, Alexander disease, lupus, anti-phospholipid syndrome, lysosomal storage disorders, fibromyalgia, Machado-Joseph disease, acyl-CoA dehydrogenase deficiency, and Leber’s optic neuropathy.

show abstract

“…Most MADD patients are of type III, which tends to have a better prognosis. The initial onset age ranges from 6 months (9) to more than 60 years (10). Furthermore, its severity varies considerably (11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

Clinical Presentations and Genetic Characteristics of Late-Onset MADD Due to ETFDH Mutations in Five Patients: A Case Series

Tang

Gao

et al. 2021

Front. Neurol.

View full text Add to dashboard Cite

Background: Late-onset multiple acyl-CoA dehydrogenase deficiency (LO-MADD) describes a curable autosomal recessive genetic disease caused by ETFDH mutations that result in defects in ETF-ubiquinone oxidoreductase. Almost all patients are responsive to riboflavin. This study describes the clinical presentations and genetic characteristics of five LO-MADD patients.Methods: From 2018 to 2021, we collected clinical and genetic data on five patients diagnosed with LO-MADD at our hospital and retrospectively analyzed their clinical characteristics, laboratory examination, electromyography, muscle biopsy, genetic analysis, and outcome data.Results: This study included three males and two females with mean onset age of 37.8 years. Fluctuating exercise intolerance was the most common presentation. Serum creatine kinase (CK) levels were significantly elevated in all patients, and plasma acylcarnitine profiles revealed an increase in long-chain acylcarnitine species in three cases. The urinary organic acid study revealed a high level of hydroxyglutaric acid in all patients. Electrophysiology demonstrated myogenic impairment. Muscle biopsies revealed lipid storage myopathy. Molecular analysis identified nine mutations (three novels and six reported) in ETFDH. Exercise intolerance and muscle weakness were dramatically improved in all patients treated with riboflavin (100 mg) daily following diagnosis.Conclusions: LO-MADD is caused by ETFDH variants and responds well to riboflavin. Three novel ETFDH pathogenic variants were identified, expanding their spectrum in the Chinese population and facilitating future interpretation and analysis of ETFDH mutations.

show abstract

A systematic review of late-onset and very-late-onset multiple acyl-coenzyme A dehydrogenase deficiency: Cohort analysis and patient report from Taiwan

Cited by 8 publications

References 24 publications

An unusual presentation of type III late onset multiple-acyl-CoA dehydrogenase deficiency leading to a review of its classification system

An unusual presentation of type III late onset multiple-acyl-CoA dehydrogenase deficiency leading to a review of its classification system

Coenzyme Q10: Role in Less Common Age-Related Disorders

Clinical Presentations and Genetic Characteristics of Late-Onset MADD Due to ETFDH Mutations in Five Patients: A Case Series

Contact Info

Product

Resources

About