Abstract
Glutaric acidemia type I (GA-I) is a treatable autosomal recessive disorder of lysine, hydroxylysine, and tryptophan metabolism caused by glutaryl-CoA dehydrogenase (GCDH) deficiency. Presentation and progression of disease are variable ranging from asymptomatic carrier state to catastrophic encephalopathy. GA-I usually presents before age 18 months, usually triggered by childhood infection, with mild or severe acute encephalopathy, striatal degeneration, and movement disorder, most often acute dystonia. At a presymptomatic stage diagnosis is suggested clinically by macrocephaly, radiologically by widened Sylvian fissures and biochemically by the presence of excess 3-hydroxyglutaric acid and glutaric acid in urine. Treatment consists of lysine-restricted diet and carnitine supplementation, specific diet restrictions, as well as symptomatic and anticatabolic treatment of intercurrent illness. Presymptomatic diagnosis and treatment are essential to prognosis. We report the case of 16-year-old macrocephalic female with late-onset GA-I and unusual paucisymptomatic presentation with fainting after exercise and widespread white matter signal changes at MRI. She was compound heterozygote for a novel mutation (IVS10-2A>G) affecting splicing at GCDH and a common missense mutation (c. 1240C>T; p.Arg402Trp, R402W). Interestingly, the site of the novel mutation is the nucleotide position of a common mutation found almost exclusively in patients of Chinese/Taiwanese origin (IVS10-2A>C).
Competing interests: None declared
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Communicated by: Georg Hoffmann
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All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from the patient included in this study. Proof that informed consent has been obtained is available upon request.
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Author Contributorship Statement
Matthew J Fraidakis: conception and design, analysis, and interpretation of data, writing/drafting of the manuscript, final approval of article.
Chrissa Liadinioti: data acquisition.
Argyris Dinopoulos: data acquisition, analysis, and interpretation of data.
Matilda Papathanassiou: data acquisition, analysis, and interpretation of data.
Judit Garcia-Villoria: data acquisition, analysis, and interpretation of data.
Antonia Ribes: data acquisition, analysis, and interpretation of data.
Roser Pons: conception and design, analysis, and interpretation of data, final approval of article.
Leonidas Stefanis: conception and design, analysis, and interpretation of data, final approval of article.
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Fraidakis, M.J. et al. (2014). Rare Late-Onset Presentation of Glutaric Aciduria Type I in a 16-Year-Old Woman with a Novel GCDH Mutation. In: Zschocke, J., Baumgartner, M., Morava, E., Patterson, M., Rahman, S., Peters, V. (eds) JIMD Reports, Volume 18. JIMD Reports, vol 18. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2014_353
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DOI: https://doi.org/10.1007/8904_2014_353
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