Chorea-Acanthocytosis
History - Nomenclature
"Neuroacanthocytosis Syndromes"
1960s Levine-Critchley syndrome
1970-2001 Neuroacanthocytosis
2001-2017 Chorea-acanthocytosis (ChAc), McLeod syndrome, PKAN/HARP, HD-like 2
2017... The four syndromes (VPS13a, XK, JPH3, and PANK2)
VPS13 gene family overview
VPS13a (9q21)→ ChAc (2/2 loss-of-function)
VPS13b (8q22)→ Cohen
VPS13c (15q22-23)→ EOPD w/ cognitive impairment
VPS13d (1q36)→ EO dystonia, chorea, and spastic ataxia
-Lipid transport regulation, 13d is mitochondrial stabilization
-13a protein=chorein
Clinical manifestations
-Rare, but likely underdiagnosed 2/2 overlap
-AR
-Typical 20-40yo
-Key dx triad chorea + acanthocytosis (smear) + ↑CK
-Progressive, mean duration 11y
-Common presentation: abnormal facial movements and lip biting
Chorea distribution
-difficulty to keep food in mouth, later limb involvement
-Self-mutilating behavior
Acanthocyte (Spur)
-Acanthocyte (narrow-base) ≠ echinocyte (large-base)
>5-50%, if absent, repeat smear
>Acanthocyte proportion not correlate w/ disease severity
>Prefer dilute instead of dry
>Abnormal Lyn kinase
Laboratory
-↑CK, LDH, and liver enzymes
-Western blot→ loss of chorein [cover figure]
-Check VPS13a, Labcorp/Invitae panels
Neuroimaging
-Caudate atrophy, use HD parameters
-Possible, T2 signal inc in caudate & putamen or iron deposition
-Rare, hippocampal sclerosis
Videos
Rubber man
-Truncal instability and sudden, violent trunk spasmsRubber man
≠Functional
Rubber man
-occasional loss of muscle tone in LE leading to gait instability
Rubber man
-appearing flaccid or unsupported while walking
Dystonic rubber man
Head drops
-Sudden loss of extensor tone in post cervical region
-Exaggerate chorea with extend & lowering the arms
-Trick→ cross arm over chest/ cross behind the neck
Trunk drops
Feeding dystonia
-common presentation
Feeding dystonia
-Tongue protrusion & jaw opening occur when she places a morsel of food in her mouth
Feeding dystonia
-Action-induced tongue protrusion while eating
Feeding dystonia
-VFSS sequence shows feeding & chewing interrupted by tongue protrusion dystonia, with subsequent normal pharyngeal & esophageal phases
Jaw-opening dystonia
-years after PD sx
Co-variations
VPS13a and JPH3
-same phenotype as VPS13a
Ddx
-McLeod syndrome
-HD
-WD
-Drug-induced DKN
-DRPLA, PKAN, NBIA
Ttx
-Feeding difficulties
>G-tube
-Chorea symptomatics
>DBS STN/GPi
-Anti-seizure medicaitons
-DMT
>Nilotinib?