Patient 1, a man of Mexican heritage, developed sniffing tics at age 32, progressing to involuntary limb and mouth movements, dementia, hallucinations, and mood disturbances. Examination revealed anarthric speech, slowed saccades, dystonia, chorea, bradykinesia, and wide-based gait. Brain MRI showed generalized atrophy. Genetic testing for C9orf72, Whole Exome Sequencing (WES), and a comprehensive ataxia panel were negative. HDL2 testing at age 41 revealed 15 and 47 CTG repeats in the JPH3 gene. Management included Buspirone, Clonazepam, and Olanzapine for anxiety, sleep, and irritability, while tetrabenazine effectively treated chorea.
Patient 2, another man with Mexican ancestry, developed leg stereotypy at 23, advancing to head jerking, involuntary limb movements, dementia, and mood disturbances. Exam was notable for dysarthria, slowed saccades, chorea, dystonia, bradykinesia, and wide-based gait. Laboratory workup showed elevated Ma2, GAD65, and DNER antibodies on a serum paraneoplastic panel, though further workup with repeat serum antibody testing, cerebrospinal fluid testing, and cancer screening was negative. Brain MRI revealed generalized atrophy. Genetic tests for HD, Friedreich Ataxia, and Spinocerebellar Ataxia panel were negative. HLD2 testing at age 62 returned positive with 15 and 45 CTG repeats in the JPH3 gene. Treatment included Risperidone, Rivastigmine, Gabapentin, and Sertraline, with Botox injections alleviating limb dystonia.
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There are few reported cases of HDL2 in the North American population. Because testing for HDL2 is predominantly recommended in patients with African ancestry, there was delayed HDL2 diagnosis in both patients due to lack of apparent African ancestry. We propose earlier HDL2 testing for HD phenocopies without known African ancestry.