TY  - JOUR
AU  - Buchberger, Anne
AU  - Riedel, Evamaria
AU  - Hackenberg, Marie
AU  - Mensch, Alexander
AU  - Beck-Woedl, Stefanie
AU  - Park, Joohyun
AU  - Haack, Tobias B
AU  - Haslinger, Bernhard
AU  - Kirschke, Jan
AU  - Prokisch, Holger
AU  - Hermann, Andreas
AU  - Mawrin, Christian
AU  - Danek, Adrian
AU  - Schoser, Benedikt
AU  - Peikert, Kevin
AU  - Deschauer, Marcus
AU  - Cordts, Isabell
TI  - The Diverse Neuromuscular Spectrum of VPS13A Disease.
JO  - Annals of Clinical and Translational Neurology
VL  - 13
IS  - 1
SN  - 2328-9503
CY  - Chichester [u.a.]
PB  - Wiley
M1  - DZNE-2026-00057
SP  - 157 - 169
PY  - 2026
AB  - VPS13A disease (chorea-acanthocytosis) is a rare neurodegenerative disorder caused by biallelic variants in VPS13A, typically presenting with hyperkinetic movement disorders, while neuromuscular signs are often mild. The aim of the project was to investigate the frequency and severity of neuromuscular impairment in VPS13A disease.We systematically assessed the neuromuscular involvement in six patients with VPS13A disease. Our evaluation included genetic and clinical data, blood tests, electrophysiological studies, muscle MRI, and tissue samples from muscle and nerve.Age at clinical onset was 14 to 38 years (median: 37.5). Age at onset of paresis was 27 to 29 years (median: 29). Initial symptoms included seizures (5/6), hyperkinesia (2/6), and muscle weakness (1/6). Neuromuscular signs ranged from hyporeflexia (5/6) to progressive muscle wasting (3/6). Nine VPS13A variants were detected, including a novel copy-neutral inversion. Phosphocreatine kinase was elevated in all cases (498-12,420 U/L; median of highest values: 2230 U/L). Nerve conduction studies revealed sensorimotor axonal neuropathy. Electromyography showed chronic neurogenic changes with high amplitudes, polyphasic potentials, and reduced interference patterns (6/6). Muscle MRI displayed fatty atrophy, most prominently in the calves (5/5). Muscle histology indicated neurogenic and myopathic changes. Electron microscopy of mitochondria and respiratory chain analysis showed no specific pathological findings.Our findings emphasize the underrecognized neuromuscular spectrum in VPS13A disease, ranging from subclinical signs to severe paresis and sometimes preceding the hyperkinesia that gave rise to the historical term of chorea-acanthocytosis. A comprehensive understanding of the phenotype is crucial for early diagnosis and appropriate management of VPS13A disease.
KW  - Humans
KW  - Adult
KW  - Male
KW  - Neuroacanthocytosis: genetics
KW  - Neuroacanthocytosis: physiopathology
KW  - Neuroacanthocytosis: pathology
KW  - Neuroacanthocytosis: complications
KW  - Female
KW  - Young Adult
KW  - Adolescent
KW  - Vesicular Transport Proteins: genetics
KW  - VPS13A protein, human (NLM Chemicals)
KW  - Vesicular Transport Proteins (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:41030128
C2  - pmc:PMC12790172
DO  - DOI:10.1002/acn3.70198
UR  - https://pub.dzne.de/record/283178
ER  -