Abstract
Background: Biallelic mutations in DNAJC12 were recently identified as a BH4-responsive cause of hyperphenylalaninemia (HPA). Outcome was only favorable when treatment was initiated early in life. We report on a 15-year-old boy with HPA due to a homozygous deletion in DNAJC12 in whom – despite his advanced age – treatment was initiated.
Case: A boy with developmental delay, an extrapyramidal movement disorder, and persistently elevated plasma phenylalanine levels was diagnosed with DNAJC12 deficiency at the age of 15 years. Diagnosis was made upon exome reanalysis revealing a homozygous 6.9 kb deletion in DNAJC12 which had not been detected by the standard exome analysis pipeline. Treatment with the BH4 analog sapropterin dihydrochloride (10 mg/kg/day) was initiated and evoked a 50% reduction of the plasma phenylalanine levels. More strikingly, a marked improvement in daily functioning and improved exercise tolerance was noted. Additionally, gait analysis before and after treatment initiation revealed a partial normalization of his movement disorder.
Conclusion: Patients with hyperphenylalaninemia due to DNAJC12 deficiency may benefit from treatment with a BH4 analog – even when introduced at a later age.
“Monique G. M. de Sain-van der Velden” and “Willemijn F. E. Kuper” contributed equally to this work.
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Communicated by: Martina Huemer, M.D.
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Synopsis
Treatment with a BH4-analog only in a patient with DNAJC12 deficiency diagnosed in puberty has a beneficial effect.
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Conflict of Interest
Monique G. M. de Sain-van der Velden, Willemijn F. E. Kuper, Marie-Anne Kuijper, Lenneke A. T. van Kats, Hubertus C. M. T. Prinsen, Astrid C. J. Balemans, Gepke Visser, Koen L. I. van Gassen, and Peter M. van Hasselt declare that they have no conflict of interest.
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Parents provided informed consent prior to article submission to use their child’s history information, metabolic and genetic test results and photographs. Signed consent form for publication was obtained.
This article does not contain any studies with human or animal subjects performed by any of the authors.
Details of the Contributions of Individual Authors
Monique de Sain-van der Velden performed the metabolic investigations and drafted and revised the manuscript.
Willemijn Kuper supported Peter van Hasselt in the clinical care for the patient and drafted and revised the manuscript.
Marie-Anne Kuijper is the rehabilitation physician who provided clinical care for the patient in the rehabilitation center, contributed to the figure and revised the manuscript.
Koen van Gassen performed the genetic investigation that demonstrated the homozygous deletions in DNAJC12 and revised the manuscript.
Lenneke van Kats performed the movement analyses contributing to the figure and revised the manuscript.
Astrid Balemans performed the movement analyses contributing to the figure and revised the manuscript.
Gepke Visser supported Peter van Hasselt in the clinical care for the patient and revised the manuscript.
Berthil Prinsen contributed in the metabolic investigations and revised the manuscript.
Peter van Hasselt is the pediatrician metabolic diseases who provided clinical care for the patient and revised the manuscript.
Corresponding Author
Peter M. van Hasselt.
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de Sain-van der Velden, M.G.M. et al. (2018). Beneficial Effect of BH4 Treatment in a 15-Year-Old Boy with Biallelic Mutations in DNAJC12. In: Morava, E., Baumgartner, M., Patterson, M., Rahman, S., Zschocke, J., Peters, V. (eds) JIMD Reports, Volume 42. JIMD Reports, vol 42. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2017_86
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DOI: https://doi.org/10.1007/8904_2017_86
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