Clinical and genetical heterogeneity of late-onset multiple acyl-coenzyme A dehydrogenase deficiency
Abstract: Background
Multiple 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.
Methods
All 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.
Results
Mean 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.
Conclusions
Late-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
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Notes
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Orphanet journal of rare diseases. 9 (2014), 117, DOI 10.1186/s13023-014-0117-5, ISSN: 1750-1172
- Keyword
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Myasthenie
Vitamin B2
- Event
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Veröffentlichung
- (where)
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Freiburg
- (who)
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Universität
- (when)
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2017
- Creator
- DOI
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10.1186/s13023-014-0117-5
- URN
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urn:nbn:de:bsz:25-freidok-125100
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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25.03.2025, 1:48 PM CET
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
Time of origin
- 2017
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