LAUSR

A 47-year-old man with a 2-year history of WD presented with increased drooling. His diagnosis was based on clinical findings (including Kayser-Fleischer rings), laboratory tests (low serum ceruloplasmin, increased 24-hr urine copper excretion), and genetic test. Sanger sequencing of the ATP7B gene showed compound heterozygosity for two pathogenic point mutations: c.2827G > A (has been described before) and c.1630C > T (novel variant leading to the termination of the protein synthesis). The Global Assessment Scale for Wilson Disease score was the following: tier 1—L1, C3, M3, O0*; tier 2—25. On examination, apart from marked parkinsonism with severe postural instability and mild limitation of the eye movements in upgaze that were present at the previous examination a year ago, continuous symmetric rhythmic involuntary movement of the lower facial muscles, soft palate, and larynx was found. By observing his irregular breathing movements of the abdominal wall, diaphragmal involvement in the hyperkinesis could be suspected as well (Video S1). According to patient, those involuntary movements developed 8 months earlier; however, they did not bother him. His caregiver reported that the movements were persistent during sleep. Patient’s medical treatment was stable for the last 8 months and included 500 mg penicillamine/ daily, pyridoxine 25 mg, elementary zinc 80 mg/daily, levodopa 300 mg/daily, and biperiden 6 mg/daily. His liver function was compensated, urinary copper excretion test showed 230 mcg/day, which indicated a relatively adequate penicillamine dose. Previous attempts to slightly increase penicillamine dose led to the exacerbation of the neurological deficit (trientine is not available in Russia). In comparison with previous 2-year-old brain MRI, which showed bilateral T2 and FLAIR hyperintensities in the dorsal midbrain and pons, atrophy of the middle cerebellar peduncles, as well as mild T2 bilateral hypointensities in the globus pallidus (Fig. 1A–1D), the repeated brain MRI showed marked increase of the midbrain and dorsal pons atrophy, bilateral symmetric HOD, and bilateral T2* hypointensities in substantia nigra, red, and dentate nuclei (Fig. 1E–1H). Bilateral symmetric HOD corresponded with the new clinical findings. To exclude other possible genetic causes of bilateral HOD, we did a next generation sequencing-based gene panel test with 723 genes included, which just confirmed ATP7B mutations but did not show any pathogenic variants in POLG, SURF1, or GFAP genes.