Project description: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.
Project description:Background and purposeAn intracranial vertebral artery dissecting aneurysm (iVADA) increases the risk of future subarachnoid hemorrhage, which is a severe complication with high rebleeding rates and poor outcomes. Identifying potential risk factors associated with iVADA growth is crucial for their effective management.MethodsThis observational study was carried out at a single center and included patients who had been diagnosed with iVADA based on neuroimaging findings. We divided the patients into two groups: with and without iVADA growth. Growth was defined as any enlargement of a dilated region or a morphological change in follow-up imaging. We measured the vertebral artery tortuosity index (VTI) in the contralateral vertebral artery (VA), defined as its actual length divided by its straight length. We investigated the factors associated with iVADA growth.ResultsThis study included 124 patients. The median follow-up period was 7 months. We observed iVADA growth in 54 patients (43.5%), who were more likely to be current smokers (33.3% vs. 14.3%, p=0.012) and have a higher VTI (1.14±0.11 [mean±standard deviation] vs. 1.06±0.12, p=0.035) compared with those without iVADA growth. A multivariate analysis revealed that the VTI (adjusted odds ratio=28.490, 95% confidence interval=1.025-792.046, p=0.048) was independently associated with iVADA growth.ConclusionsThis study has identified an independent association between VA tortuosity and iVADA growth.