Beneficial effect of BH4 treatment in a 15-year-old boy with biallelic mutations in DNAJC12

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, Peter M. van Hasselt

Research output: Chapter in Book/Report/Conference proceedingChapterAcademicpeer-review

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.
Original languageEnglish
Title of host publicationJIMD Reports
PublisherSpringer
Pages99-103
Volume42
DOIs
Publication statusPublished - 2018

Publication series

NameJIMD Reports
ISSN (Print)2192-8304
ISSN (Electronic)2192-8312

Cite this

de Sain-van der Velden, M. G. M., Kuper, W. F. E., Kuijper, M-A., van Kats, L. A. T., Prinsen, H. C. M. T., Balemans, A. C. J., ... van Hasselt, P. M. (2018). Beneficial effect of BH4 treatment in a 15-year-old boy with biallelic mutations in DNAJC12. In JIMD Reports (Vol. 42, pp. 99-103). (JIMD Reports). Springer. https://doi.org/10.1007/8904_2017_86
de Sain-van der Velden, Monique G. M. ; Kuper, Willemijn F. E. ; Kuijper, Marie-Anne ; van Kats, Lenneke A. T. ; Prinsen, Hubertus C. M. T. ; Balemans, Astrid C. J. ; Visser, Gepke ; van Gassen, Koen L. I. ; van Hasselt, Peter M. / Beneficial effect of BH4 treatment in a 15-year-old boy with biallelic mutations in DNAJC12. JIMD Reports. Vol. 42 Springer, 2018. pp. 99-103 (JIMD Reports).
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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.",
author = "{de Sain-van der Velden}, {Monique G. M.} and Kuper, {Willemijn F. E.} and Marie-Anne Kuijper and {van Kats}, {Lenneke A. T.} and Prinsen, {Hubertus C. M. T.} and Balemans, {Astrid C. J.} and Gepke Visser and {van Gassen}, {Koen L. I.} and {van Hasselt}, {Peter M.}",
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de Sain-van der Velden, MGM, Kuper, WFE, Kuijper, M-A, van Kats, LAT, Prinsen, HCMT, Balemans, ACJ, Visser, G, van Gassen, KLI & van Hasselt, PM 2018, Beneficial effect of BH4 treatment in a 15-year-old boy with biallelic mutations in DNAJC12. in JIMD Reports. vol. 42, JIMD Reports, Springer, pp. 99-103. https://doi.org/10.1007/8904_2017_86

Beneficial effect of BH4 treatment in a 15-year-old boy with biallelic mutations in DNAJC12. / de Sain-van der Velden, Monique G. M.; Kuper, Willemijn F. E.; Kuijper, Marie-Anne; van Kats, Lenneke A. T.; Prinsen, Hubertus C. M. T.; Balemans, Astrid C. J.; Visser, Gepke; van Gassen, Koen L. I.; van Hasselt, Peter M.

JIMD Reports. Vol. 42 Springer, 2018. p. 99-103 (JIMD Reports).

Research output: Chapter in Book/Report/Conference proceedingChapterAcademicpeer-review

TY - CHAP

T1 - Beneficial effect of BH4 treatment in a 15-year-old boy with biallelic mutations in DNAJC12

AU - de Sain-van der Velden, Monique G. M.

AU - Kuper, Willemijn F. E.

AU - Kuijper, Marie-Anne

AU - van Kats, Lenneke A. T.

AU - Prinsen, Hubertus C. M. T.

AU - Balemans, Astrid C. J.

AU - Visser, Gepke

AU - van Gassen, Koen L. I.

AU - van Hasselt, Peter M.

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

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UR - https://www.ncbi.nlm.nih.gov/pubmed/29380259

U2 - 10.1007/8904_2017_86

DO - 10.1007/8904_2017_86

M3 - Chapter

VL - 42

T3 - JIMD Reports

SP - 99

EP - 103

BT - JIMD Reports

PB - Springer

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de Sain-van der Velden MGM, Kuper WFE, Kuijper M-A, van Kats LAT, Prinsen HCMT, Balemans ACJ et al. Beneficial effect of BH4 treatment in a 15-year-old boy with biallelic mutations in DNAJC12. In JIMD Reports. Vol. 42. Springer. 2018. p. 99-103. (JIMD Reports). https://doi.org/10.1007/8904_2017_86