TY - CHAP
T1 - Beneficial Effect of BHTreatment 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 - 2018/1/30
Y1 - 2018/1/30
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.
KW - DNAJC12
KW - Hyperphenylalaninemia
KW - Sapropterin dihydrochloride
KW - Tetrahydrobiopterin
KW - Treatment
UR - http://www.scopus.com/inward/record.url?scp=85056933105&partnerID=8YFLogxK
U2 - 10.1007/8904_2017_86
DO - 10.1007/8904_2017_86
M3 - Chapter
C2 - 29380259
SN - 978-3-662-58364-7
VL - 42
T3 - JIMD Reports
SP - 99
EP - 103
BT - JIMD Reports
A2 - Morava, Eva
A2 - Baumgartner, Matthias
A2 - Patterson, Marc
A2 - Rahman, Shamima
A2 - Zschocke, Johannes
A2 - Peters, Verena
PB - Springer
ER -