Neuromuscular Involvement in Choreoacanthocytosis (P07.204)

Abstract

Objective: To further describe the peripheral nervous system involvement in choreoacanthocytosis (ChAc) by reporting the findings in 7 patients. Background ChAc is characterized by involuntary movements, behavioral changes, seizures, and hyperCKmia together with peripheral blood acanthocitosis, caused by mutations in the VPS13A gene. Little is known so far about the neuromuscular involvement in these patients, although myopathic or neurogenic changes have been reported in single cases. Design/Methods: We studied 7 patients from 4 unrelated families. Three patients were referred to role out mitochondrial myopathy. ChAc diagnosis was made according to clinical criteria, chorein western-blot and expression of Kell antigen. Clinical examination, conduction nerve studies, electromyography, muscle magnetic resonance imaging (MRI) T1/ STIR sequences of lower limbs and biopsy of distal (gastrocnemius/tibialis anterior) and proximal (biceps braquii) muscles were performed. Informed consent was obtained for inclusion in the study. Results: Clinical examination showed asymmetric calf atrophy in two patients, but was otherwise unremarkable. The serum CK level was elevated and fluctuating (range 275-4050 UI/l). The conduction studies showed decrease in the amplitude of sensory sural nerve potential. Electromyography revealed a mild neurogenic pattern. Western-blot for chorein in peripheral blood showed absence or severe decreased of protein level. T1-sequences MRI showed symmetric increased signal in both gastrocnemius. STIR-sequences were normal. Biopsies of proximal muscles showed subtle changes, while biopsies of distal muscles showed striking neurogenic atrophy together with necrosis and regeneration. Focal areas of myofibrillar disorganization were noted. Conclusions: The selective radiological involvement of gastrocnemius and the coexistence of neurogenic and myopathic features in gastrocnemius biopsy seem to be characteristic features of ChAc which could be helpful for diagnosis. In our study population, neuromuscular involvement was clinically irrelevant. The complexity of this syndrome usually delays the diagnosis of ChAc. Disclosure: Dr. Paradas Lopez has nothing to disclose. Dr. Cabrera Serrano has nothing to disclose. Dr. Rivas Infante has nothing to disclose. Dr. Morales has nothing to disclose. Dr. Marquez has nothing to disclose. Dr. Bader has nothing to disclose. Dr. Mir has nothing to disclose.