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:A 23-year-old man with recurrent acute myeloid leukemia (AML) underwent successful reinduction and was judged posttherapy to be in complete remission. Soon thereafter, he complained of pain in his left buttock radiating into his left posterior thigh. Neurologic examination was unremarkable. Radiographic evaluation demonstrated a left S2 lesion suggestive of a nerve sheath tumor (figure 1). An open biopsy was performed that revealed a chloroma pathologically (figure 2), sometimes referred to as a myeloid sarcoma.(1,2) Most chloromas are found in patients with recurrent AML and are overwhelmingly intracranial.(1) Infrequently, chloromas are paraspinal, and in this location present with epidural spinal cord compression.(2) Intraspinal invasion by a chloroma is rare. Systemic evaluation confirmed recurrent AML, for which he was successfully treated with reinduction and whole-body irradiation followed by an allogeneic transplant. He is currently disease-free and neurologically asymptomatic 1 year posttransplant.