Abstract
Background: Dilated cardiomyopathy (DCM), non-progressive cerebellar ataxia (A), testicular dysgenesis, growth failure, and 3-methylglutaconic aciduria are the hallmarks of DNAJC19 defect (or DCMA syndrome) due to biallelic mutations in DNAJC19. To date DCMA syndrome has been reported in 19 patients from Canada and in two Finnish siblings. The underlying pathomechanism is unknown; however, DNAJC19 is presumed to be involved in mitochondrial membrane related processes (e.g., protein import and cardiolipin remodeling). Here, we report an additional patient with progressive cerebellar atrophy and white matter changes.
Patient and Methods: A Turkish boy presented at age 2 months with dilated cardiomyopathy (initially worsening then stabilizing in the second year of life), growth failure, bilateral cryptorchidism, and facial dysmorphism. Mental and motor developmental were, respectively, moderately and severely delayed. Profound intentional tremor and dyskinesia, spasticity (particularly at the lower extremities), and dystonia were observed. Sensorineural hearing loss was also diagnosed. MRI showed bilateral basal ganglia signal alterations. Plasma lactate levels were increased, as was urinary excretion of 3-methylglutaconic acid. He deceased aged 3 years.
Results: Sanger Sequencing of DNAJC19 confirmed the clinical diagnosis of DNAJC19 defect by revealing the previously unreported homozygous stop mutation c.63delC (p.Tyr21*). Investigation of enzymes of mitochondrial energy metabolism revealed decreased activity of cytochrome c oxidase in muscle tissue.
Discussion: Sensorineural hearing loss and bilateral basal ganglia lesions are common symptoms of mitochondrial disorders. This is the first report of an association with DNAJC19 defect.
Mahmut Çoker and Saskia B. Wortmann contributing equally to this manuscript.
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Communicated by: Garry Brown
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Synopsis
Sensorineural hearing loss and bilateral basal ganglia lesions may be additional features of dilated cardiomyopathy and ataxia syndrome.
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Sema Kalkan Ucar, Johannes A. Mayr, René G. Feichtinger, Ebru Canda, Mahmut Çoker, and Saskia B. Wortmann declare that they have no conflict of interest.
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Author Contributions
Sema Kalkan Ucar diagnosed the patient, drafted the manuscript, reviewed the literature, and approved final version of the manuscript.
Johannes A. Mayr performed the laboratory investigations, drafted laboratory information details, and approved final version of the manuscript.
René G. Feichtinger performed the laboratory investigations, drafted laboratory information details, and approved final version of the manuscript.
Ebru Canda participated in the clinical follow-up of the patient and approved final version of the manuscript.
Mahmut Çoker is a senior clinician and provided supervision in data analysis and completing the manuscript.
Saskia B. Wortmann is a senior clinician and provided supervision in data analysis and completing the manuscript.
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Ucar, S.K., Mayr, J.A., Feichtinger, R.G., Canda, E., Çoker, M., Wortmann, S.B. (2016). Previously Unreported Biallelic Mutation in DNAJC19: Are Sensorineural Hearing Loss and Basal Ganglia Lesions Additional Features of Dilated Cardiomyopathy and Ataxia (DCMA) Syndrome?. In: Morava, E., Baumgartner, M., Patterson, M., Rahman, S., Zschocke, J., Peters, V. (eds) JIMD Reports, Volume 35. JIMD Reports, vol 35. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2016_23
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DOI: https://doi.org/10.1007/8904_2016_23
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