{
  "abstract": "Background Variants in the vaccinia-related kinase 1 (VRK1) gene have been linked to a spectrum of lower motor neuron disorders, typically characterised by distal muscle weakness and atrophy. Homozygous c.961C>T (p.Arg321Cys) is a rare mutation associated with a slowly progressive distal spinal muscular atrophy phenotype, usually presenting with normal or mildly elevated creatine kinase (CK) levels.Case presentation A 29-year-old man born to consanguineous parents presented with a 2 year history of progressive lower limb weakness. Examination revealed distal lower limb muscle wasting, absent ankle reflexes and brisk knee and upper limb reflexes. CK was elevated at 17 791 IU/L (normal<190). Neurophysiology showed a motor neuropathy with chronic active denervation, and MRI showed fatty atrophy and oedema in lower limb muscles. Muscle biopsies revealed neurogenic atrophy, scattered necrotic myofibres, pseudo-dystrophic changes and reduced sarcolemmal dysferlin. Genetic testing identified a homozygous VRK1 (c.961C>T, p.Arg321Cys) variant.Conclusions This report expands the VRK1 phenotype to include marked hyperCKaemia. Elevated CK levels are typically associated with inflammatory myopathies, though they can be seen in primary diseases of the motor neurons. A lack of sarcolemmal dysferlin could underlie myofibre sensitivity to minor trauma and cause elevated CK levels in chronic muscle denervation.",
  "authors": [
    {
      "affiliations": [
        "Westmead Clinical School, The University of Sydney, Sydney, New South Wales, Australia"
      ],
      "name": "Himath Siriniwasa"
    },
    {
      "affiliations": [
        "Central Clinical School, The University of Sydney, Sydney, New South Wales, Australia"
      ],
      "name": "Macken James Laurence Stirling"
    },
    {
      "affiliations": [
        "Neurology Department, Westmead Hospital, Westmead, New South Wales, Australia"
      ],
      "name": "Siobhan Kean"
    },
    {
      "affiliations": [
        "Neuropathology, Royal Prince Albert Hospital, Camperdown, New South Wales, Australia"
      ],
      "name": "Roger Pamphlett"
    },
    {
      "affiliations": [
        "Westmead Clinical School, The University of Sydney, Sydney, New South Wales, Australia",
        "Neurology Department, Westmead Hospital, Westmead, New South Wales, Australia"
      ],
      "name": "Matthew Silsby"
    }
  ],
  "title": "Severe hyperCKaemia and decreased sarcolemmal dysferlin in VRK1-associated distal spinal muscular atrophy: a case report",
  "uid": "10c8b8d3-03af-52d0-ae66-5e4c4c37dd26"
}