McLeod syndrome in an Italian patient

Introduction: McLeod syndrome (MLS) is a rare X-linked multisystem disorder caused by mutations in the XK gene, encoding the Kx antigen on red blood cells. Peculiar laboratory findings are acanthocytosis and McLeod blood-group phenotype. The disease includes CNS features similar to Huntington's disease and neuromuscular manifestations. Patient and methods: We report the case of a 52-year old patient with moderate dysarthria, scratching skin lesions, limb hypotonia and muscle wasting with reduced tendon reflexes, diffuse choreic movements with prominent orolingual dyskinesias and walk instability. He had a family history of chorea and seizures in the maternal grandfather, whilst both his parents and his sister did not show any neurological anomaly. Brain MRI revealed caudate atrophy. Electromyography and nerve conduction study suggested sensory-motor axonal polyneuropathy of lower limbs. Blood tests showed prominent CK elevation. We also observed the presence of acanthocytes. RBC immunohematological examination showed no Kpa/Kpb antigens and extremely reduced expression of Kell surface protein, consistent with "McLeod blood group phenotype". Genetic analysis was performed by direct sequencing of the three XK gene exons and the intron-exon boundaries. Results: Molecular screening of the XK gene revealed the hemizygous five-base deletion c.856_860delCTCTA, in exon 3. This mutation was previously referred as 938-942delCTCTA. Conclusions: This is the first Italian case of MLS caused by a small deletion in exon 3 of the XK gene. This deletion creates a premature stop codon. Although there is not a clear genotype-phenotype correlation, molecular characterization is the gold standard in diagnosis and further classification of the syndrome.