Central nervous system and muscle involvement in an adolescent patient with riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency

Ishii, Kiyoko; Komaki, Hirofumi; Ohkuma, Aya; Nishino, Ichizo; Nonaka, Ikuya; Sasaki, Masayuki

doi:10.1016/j.braindev.2009.08.008

Cited by 19 publications

(8 citation statements)

References 10 publications

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“…As per FAO study, this missense mutation, which has been previously identified in patients with MADD [6,12] affects the function of the ETFDH protein. Several reports have documented marked improvement in symptoms in ETFDH deficiency with carnitine but also riboflavin treatment, particularly in patients with missense variants [7,9,10,11,14,15,19], Moreover, ETFDH mutations have also been reported in a myopathic form of CoQ10 deficiency effectively treated with CoQ10 supplementation.…”

Section: Discussionmentioning

confidence: 73%

Pregnancy of a patient with multiple Acyl-CoA dehydrogenation deficiency (MADD)

Trakadis

Kadlubowska

Barnes

et al. 2012

Molecular Genetics and Metabolism

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Section: Discussionmentioning

confidence: 73%

Pregnancy of a patient with multiple Acyl-CoA dehydrogenation deficiency (MADD)

Trakadis

Kadlubowska

Barnes

et al. 2012

Molecular Genetics and Metabolism

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“…The positive clinical effects of riboflavin treatment are well documented as are the molecular mechanisms for riboflavin responsiveness [[4],[7],[8],[29],[48],[49]]. In particular, the chaperone effects that can compensate for inherited folding defects of ETFDH, have recently been described [[49]].…”

Section: Discussionmentioning

confidence: 99%

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

Grünert

2014

Orphanet J Rare Dis

145

139

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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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“…As mentioned above, the previously reported zebrafish model also displayed some neural defects, including reduced motor axon branching and neuromuscular synapse number . Although the neural phenotype was not documented as a classic phenotype of MADD or studied in mammalian cells before, central nervous system involvement and sensory ataxic neuropathy have been described in patients with ETFDH mutations . Furthermore, neuropathy has been well described in several fatty acid oxidation defects, including mitochondrial trifunctional protein deficiency and very‐long‐chain and medium‐chain acyl‐CoA dehydrogenase deficiencies.…”

Section: Discussionmentioning

confidence: 94%