Christine Anna Dambietz (Münster / DE), Dr. Andrea Doescher (Institut Bremen-Oldenburg / DE), Prof. Dr. Heinz Wiendl (Münster / DE), Prof. Dr. Gerd Meyer zu Hörste (Münster / DE), Dr. Sarah Wiethoff (Münster / DE)
Abstract-Text (inkl. Referenzen)
Introduction XK gene mutations are linked with McLeod"s syndrome, a rare x-linked neuroacanthocytosis. The XK gene codes for the Kx protein which forms a heterodimer with Kell protein and supports its antigen expression. XK mutations are associated with dysfunction/ loss of Kx protein and a variable multisystemic spectrum disorder.
Methods We performed multi gene panel sequencing and CSF flow cytometry. Kell (K) and cellano (k) antigen expression was analyzed by Fluorescent Activated Cell Sorting. KEL gene expression was examined by RNA sequencing.
Results A 46-year old male presented with decrease in physical performance and persisting fatigue after COVID-19. Examinations showed raised CK levels, neuropathy and myopathy. Genetic analysis revealed a novel hemizygous frameshift deletion in the XK gene resulting in premature termination of the amino acid chain. FACS revealed the K-k+ blood type and reduced cellano density. CSF flow cytometry showed elevation of activated T cells. Additional RNA sequencing is performed with results pending.
Conclusion We present a patient with a novel frameshift deletion in the XK gene. The genetic origin of symptoms is supported by long-standing axonal neuro- and myopathy and raised CK levels prior to COVID-19. Elevated activated T-lymphocytes in CSF indicate an additional immune activation in the CNS. COVID-19 as a trigger of CNS involvement and clinical manifestation is likely, though further CSF analysis in patients with XK mutations is needed.