JIMD Reports, Volume 42

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, de Sain-van der Velden, Monique G. M., Kuper, Willemijn F. E., Kuijper, Marie-Anne, Kats, Lenneke A. T., Prinsen, Hubertus C. M. T., Balemans, Astrid C. J., Visser, Gepke, Gassen, Koen L. I., Hasselt, Peter M., Kats, Lenneke A. T. van, Gassen, Koen L. I. van, Hasselt, Peter M. van

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. 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. Patients with hyperphenylalaninemia due to DNAJC12 deficiency may benefit from treatment with a BH4 analog - even when introduced at a later age.