Rare Genetic Disorder Mimics Nerve Attack, Defying Standard Treatment
Researchers discovered that a mitochondrial gene mutation can trigger sudden paralysis that looks identical to Guillain-Barré syndrome but doesn't respond to standard immune therapy. The finding could reshape how doctors evaluate rare neurological emergencies and highlights the need for faster genetic testing in acute care settings.
Originaltitel: Homozygous FDXR variant in twin sisters with spastic paraparesis followed by acute progressive flaccid quadriparesis
FDXR-related disorders (FRDs) are rare mitochondrial conditions typically presenting with progressive optic atrophy and neuropathy. We report identical twins presenting with acute-onset flaccid quadriparesis following a respiratory infection, expanding the known phenotypic spectrum of FDXR variants. 22-year-old monozygotic twins from a consanguineous Iranian family developed progressive weakness after an upper respiratory infection, initially diagnosed as Guillain-Barré syndrome. Despite IVIG and plasmapheresis, both progressed to flaccid quadriplegia. Twin A. had additional manifestations including blindness, dysarthria, and incontinence, that were not present in Twin B. Extensive workup excluded inflammatory, infectious, and some metabolic etiologies. Whole exome sequencing (WES) revealed a homozygous FDXR missense variant (c.463C>T, p.Arg155Trp) in Twin A. This represents the first report of the mentioned FDXR variant in monozygotic twins. The twins' phenotypic discordance despite genetic identity suggests environmental or epigenetic modifiers. Our findings underscore: 1. FDXR variants should be considered in acute neuropathies unresponsive to immunotherapy. 2. The c.463C>T variant may cause both acute and chronic presentations.