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 → ChAc (2/2 loss-of-function)
VPS13b → Cohen
VPS13c → EOPD w/ cognitive impairment
VPS13d → 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%, if absent, repeat smear
>Abnormal Lyn kinase
Laboratory
-↑CK, LDH, and liver enzymes
-Western blot→ loss of chorein [cover figure]
Videos
Rubber man
-Truncal instability and sudden, violent trunk spasmsRubber man
Head drops
-Sudden loss of extensor tone in post cervical region
-Exaggerate chorea with extend & lowering the arms
Feeding dystonia
-common presentation
Co-variation
VPS13a and JPH3
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?