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Orphanet Journal of Rare Diseases

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Open Access 01-12-2014 | Research

Clinical and genetical heterogeneity of late-onset multiple acyl-coenzyme A dehydrogenase deficiency

Author: Sarah C Grünert

Published in: Orphanet Journal of Rare Diseases | Issue 1/2014

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.

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Title: Clinical and genetical heterogeneity of late-onset multiple acyl-coenzyme A dehydrogenase deficiency
Author: Sarah C Grünert
Publication date: 01-12-2014
Publisher: BioMed Central
Published in: Orphanet Journal of Rare Diseases / Issue 1/2014
Electronic ISSN: 1750-1172
DOI: https://doi.org/10.1186/s13023-014-0117-5

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Clinical and genetical heterogeneity of late-onset multiple acyl-coenzyme A dehydrogenase deficiency

Abstract

Background

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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