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We strongly agree with Dr. Schon and Prof. Chinnery that alpha-methylacyl-CoA racemase (AMACR) deficiency should be considered in the differential diagnosis of patients presenting with combinations of stroke-like episodes, seizures, encephalopathy, and retinal pigmentary changes.1As described in our study,1causative AMACRvariants in patients with clinical features suggestive of mitochondrial disease highlight a broader issue of mitochondrial disease phenocopies that require consideration by a comprehensive sequencing approach for suspected mitochondrial disease cases. Examples of this include 3 individuals from 2 families in our study,13 individuals in the 100,000 Genomes Project,2an individual in the study by Theunissen et al,3and a recent case of an individual with late-onset disease associated with stroke-like episodes and seizures.4

A 71-year-old woman presented with a 6-week history of progressive involuntary right face and arm jerking movements associated with prominent memory loss and frequent falls. She subsequently developed similar movements involving her left face and arm. Montreal Cognitive Assessment (MoCA) score was 19/30 and physical examination was otherwise normal. There was no alteration of consciousness. A video EEG recorded bilateral clinical activity with no alteration in consciousness and no electrographic epileptiform correlate (see video at Neurology.org/cp). MRI demonstrated nonenhancing diffuse T2 hyperintensity of the hippocampal region of the left medial temporal lobe (figure). Serum and CSF were positive for voltage-gated potassium channel (VGKC) antibodies (6,534 pmol/L and 160 pmol/L, respectively). Anti-Lgi1 antibodies were strongly positive, and anti-Caspr2 antibodies were negative. Onconeuronal antibodies and paraneoplastic workup were negative; serum sodium nadir was 130 mmol/L, coinciding with cognitive nadir. She received pulsed methylprednisolone and IV immunoglobulin and responded rapidly, with involuntary movements abolished within 2 weeks. Memory improved over 2 months and function returned to baseline, although amnesia for the period of illness and retrograde amnesia extending 2 months prior persists. Her MoCA score plateaued at 27/30. IV immunoglobulin was discontinued after 2 months, and the steroid taper continues gradually. Follow-up MRI at 4 months demonstrated resolution of the left hippocampal T2 hyperintensity.