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@ARTICLE{Buchberger:283178,
author = {Buchberger, Anne and Riedel, Evamaria and Hackenberg, Marie
and Mensch, Alexander and Beck-Woedl, Stefanie and Park,
Joohyun and Haack, Tobias B and Haslinger, Bernhard and
Kirschke, Jan and Prokisch, Holger and Hermann, Andreas and
Mawrin, Christian and Danek, Adrian and Schoser, Benedikt
and Peikert, Kevin and Deschauer, Marcus and Cordts,
Isabell},
title = {{T}he {D}iverse {N}euromuscular {S}pectrum of {VPS}13{A}
{D}isease.},
journal = {Annals of Clinical and Translational Neurology},
volume = {13},
number = {1},
issn = {2328-9503},
address = {Chichester [u.a.]},
publisher = {Wiley},
reportid = {DZNE-2026-00057},
pages = {157 - 169},
year = {2026},
abstract = {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.},
keywords = {Humans / Adult / Male / Neuroacanthocytosis: genetics /
Neuroacanthocytosis: physiopathology / Neuroacanthocytosis:
pathology / Neuroacanthocytosis: complications / Female /
Young Adult / Adolescent / Vesicular Transport Proteins:
genetics / VPS13A protein, human (NLM Chemicals) / Vesicular
Transport Proteins (NLM Chemicals)},
cin = {AG Hermann},
ddc = {610},
cid = {I:(DE-2719)1511100},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:41030128},
pmc = {pmc:PMC12790172},
doi = {10.1002/acn3.70198},
url = {https://pub.dzne.de/record/283178},
}