A 62-year-old man was referred to neurology clinic for slowly progressive lower-extremity weakness and involuntary movements. His symptoms stretched back nearly a decade. Initially, he noticed subtle leg fatigue and difficulty keeping up with peers on walks. Over subsequent years, climbing stairs and tiptoeing became taxing.
Three years before presentation, however, he developed intermittent, brief shoulder elevations and episodes of lip pursing that he could not suppress. He denied dysphagia, dysarthria, diplopia, or ptosis.
These movements gradually increased in frequency, prompting medical evaluation. There was no cognitive decline, behavioral change, or seizures. His past medical history was notable for a presumed diagnosis of polymyositis, for which he had received glucocorticoids without improvement. He had no family history of neurologic or neuromuscular disease.
On examination, he was alert and cognitively intact. Cranial nerves were normal except for brief choreiform facial movements. Motor examination showed symmetric 4/5 strength in the lower limbs, predominantly proximal, with preserved bulk. Plantar flexion was disproportionately weak. Sensation, reflexes, and coordination were unremarkable. Gait was normal aside from mild difficulty rising from a chair.
Routine laboratory studies were within reference ranges except for striking hyperCKemia of 1961 U/L. Lactate dehydrogenase was modestly elevated. A peripheral smear was notable for abnormal red blood cell morphology. Electromyography revealed chronic neurogenic motor unit changes with reduced recruitment. Muscle MRI showed multifocal hyperintense lesions in the posterior thigh musculature, sparing anterior compartments. Muscle biopsy demonstrated mild fiber size variability and infrequent internal nuclei without inflammatory infiltrates or dystrophic protein loss.
Given the movement disorder, neuroimaging was obtained. Brain MRI showed no caudate atrophy or other structural abnormalities. Cardiac evaluation, including ECG and echocardiography, was normal.
The coexistence of choreiform movements, chronic myopathy, neurogenic EMG changes, and elevated CK prompted a broad differential diagnosis. Huntington disease could explain the involuntary movements but not the hyperCKemia or abnormal erythrocytes. Wilson disease was considered, yet liver tests and brain imaging were unremarkable, and ceruloplasmin was normal. Chorea-acanthocytosis was plausible given the involuntary facial movements and peripheral smear abnormalities; however, the patient lacked prominent oromandibular dyskinesias, seizures, and early reflex changes typically associated with that syndrome.
The key turning point emerged from the hematologic findings. The peripheral smear demonstrated acanthocytes, suggesting a neuroacanthocytosis syndrome. Subsequent genetic testing identified a hemizygous pathogenic variant in the XK gene, confirming the diagnosis of McLeod syndrome. In this patient, tiapride was prescribed to alleviate chorea, resulting in modest symptom improvement.
“This case underscores that MLS is a complex multisystem disorder affecting neuromuscular, hematologic, cardiovascular and CNS functions,” wrote the authors, who were led by Ye Liu, MD. “Acanthocytes in peripheral blood provides key diagnosis clues. Genetic testing confirms the diagnosis.”
The authors had no disclosures to report.
Source: JAMA Neurology
