Abstract
Background: Isobutyryl-CoA dehydrogenase (IBD) is a mitochondrial enzyme catalysing the third step in the degradation of the essential branched-chain amino acid valine and is encoded by ACAD8. ACAD8 mutations lead to isobutyryl-CoA dehydrogenase deficiency (IBDD), which is identified by increased C4-acylcarnitine levels. Affected individuals are either asymptomatic or display a variety of symptoms during infancy, including speech delay, cognitive impairment, failure to thrive, hypotonia, and emesis.Methods: Here, we review all previously published IBDD patients and describe a girl diagnosed with IBDD who was presenting with autism as the main disease feature.Results: To assess whether a phenotype-genotype correlation exists that could explain the development or absence of clinical symptoms in IBDD, we compared CADD scores, in silico mutation predictions, LoF tolerance scores and C4-acylcarnitine levels between symptomatic and asymptomatic individuals. Statistical analysis of these parameters did not establish significant differences amongst both groups.Conclusion: As in our proband, trio whole exome sequencing did not establish an alternative secondary genetic diagnosis for autism, and reported long-term follow-up of IBDD patients is limited, it is possible that autism spectrum disorders could be one of the disease-associated features. Further long-term follow-up is suggested in order to delineate the full clinical spectrum associated with IBDD.
Original language | English |
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Article number | e1595 |
Number of pages | 10 |
Journal | Molecular genetics & genomic medicine |
Volume | 9 |
Issue number | 2 |
Early online date | 11 Jan 2021 |
DOIs | |
Publication status | Published - Feb 2021 |
Keywords
- acad8
- autism
- carnitine
- children
- disorders
- encephalopathy
- follow-up
- genotype-phenotype correlation
- identification
- inborn-errors
- isobutyryl-coa dehydrogenase deficiency
- mutations
- tandem mass-spectrometry
- whole exome sequencing
- CARNITINE
- FOLLOW-UP
- MUTATIONS
- ACAD8
- isobutyryl-CoA dehydrogenase deficiency
- DISORDERS
- TANDEM MASS-SPECTROMETRY
- IDENTIFICATION
- INBORN-ERRORS
- CHILDREN
- ENCEPHALOPATHY