Christine A. Dambietz ^1* Andrea Doescher ^2* Michael Heming ¹ Anja Schirmacher ^3* Bernhard Schlüter ^3* Andreas Schulte-Mecklenbeck ¹ Christian Thomas ⁴ Heinz Wiendl ¹ Gerd Meyer Zu Horste ¹ Sarah Wiethoff ^1*

• ¹ Department of Neurology with Institute of Translational Neurology, University Hospital Münster, Münster, North Rhine-Westphalia, Germany
• ² Blutspendedienst NSTOB, Springe, Germany
• ³ University Hospital Münster, Münster, North Rhine-Westphalia, Germany
• ⁴ Institute of Neuropathology, University Hospital Münster, Münster, North Rhine-Westphalia, Germany

Introduction Pathogenic variants in the XK gene are associated with dysfunction or loss of XK protein leading to McLeod syndrome (MLS), a rare X-linked neuroacanthocytosis syndrome with multisystemic manifestation. Here we present clinical, genetic and immunological data on a patient originally admitted to our clinic for presumed post-COVID-19 syndrome, where thorough clinical work-up revealed a novel frameshift deletion in XK causal for the underlying phenotype. We additionally review the clinicogenetic spectrum of reported McLeod cases in the literature. Methods We performed in-depth clinical characterization and flow cytometry of cerebrospinal fluid (CSF) in a patient where multi-gene panel sequencing identified a novel hemizygous frameshift deletion in XK. Additionally, Kell (K) and Cellano (k) antigen expression was analysed by Fluorescenceactivated Cell Sorting (FACS). KEL gene expression was examined by RNA sequencing. Results A novel hemizygous frameshift deletion in the XK gene resulting in premature termination of the amino acid chain was identified in a 46-year old male presenting with decrease in physical performance and persisting fatigue after COVID-19 infection. Examinations showed raised creatine kinase (CK) levels, neuropathy and clinical features of myopathy. FACS revealed the K-k+ blood type and reduced Cellano density. CSF flow cytometry showed elevation of activated T cells. Conclusion In-depth clinical, genetic, immunological and ribonucleic acid (RNA) expression data revealed axonal neuropathy, myopathy and raised levels of activated CSF-T-lymphocytes in a patient with a previously unpublished frameshift deletion in the XK gene.