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Identification of patients with Pompé disease using routine pathology results: PATHFINDER (creatine kinase) study
  1. Tim M Reynolds1,
  2. Karen Tylee2,
  3. Kathryn Booth2,
  4. Anthony S Wierzbicki3
  5. PATHFINDER Project Collaboration group
    1. 1 Clinical Chemistry, Queen's Hospital, Burton-on-Trent, UK
    2. 2 Willink Biochemical Genetics Unit, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK
    3. 3 Metabolic Medicine/Chemical Pathology, Guy's & St Thomas' Hospitals, London, UK
    1. Correspondence to Prof Anthony S Wierzbicki, Chemical Pathology, St Thomas Hospital, London SE1 7EH, UK; anthony.wierzbicki{at}


    Aims Adult-onset inherited errors of metabolism can be difficult to diagnose. Some cases of potentially treatable myopathy are caused by autosomal recessive acid α-1,4 glucosidase (acid maltase) deficiency (Pompé disease). This study investigated whether screening of asymptomatic patients with elevated creatine kinase (CK) could improve detection of Pompé disease.

    Methods Pathology databases in six hospitals were used to identify patients with elevated CK results (>2× upper limit of normal). Patients were recalled for measurement of acid α-1,4 glucosidase activity in dried blood spot samples.

    Results Samples were obtained from 812 patients with elevated CK. Low α-glucosidase activity was found in 13 patients (1.6%). Patients with neutropaenia (n=4) or who declined further testing (n=1) were excluded. Confirmation plasma specimens were obtained from eight individuals (1%) for a white cell lysosomal enzyme panel, and three (0.4%) were confirmed to have low α-1,4-glucosidase activity. One patient was identified as a heterozygous carrier of an acid α-1,4 glucosidase c.-32–13 G>T mutation. Screening also identified one patient who was found to have undiagnosed Fabry disease and one patient with McArdle’s disease. One patient later presented with Pompé’s after an acute illness. Including the latent case, the frequency of cases at 0.12% was lower than the 2.5% found in studies of patients with raised CK from neurology clinics (p<0.001).

    Conclusions Screening pathology databases for elevated CK may identify patients with inherited metabolic errors affecting muscle metabolism. However, the frequency of Pompé’s disease identified from laboratory populations was less than that in patients referred for neurological investigation.

    • creatine kinase, screening
    • lysosomal acid maltase
    • alpha 1,4 glucosidase
    • glycogen storage disease
    • fabry disease
    • pompé disease

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    • Handling editor Tahir S Pillay.

    • Collaborators Dr Taruna Likhari PI, Genessa Peters RN (Hospital: Ipswich Hospital; number of recruits: 139); Dr Nicky McRobert PI/RN, Jamie Burbage RN (Oxford University Hospital; number of recruits: 53); Dr Nigel Capps PI, Louise Tonks RN (Princess Royal, Telford; number of recruits: 88); Professor Tim Reynolds PI, Jane Reynolds RN, Clare Mewles study admin (Queen's Hospital, Burton; number of recruits: 330); Ms Jackie Smith PI (Russells Hall Hospital, Dudley; number of recruits: 139); Dr Anthony Fryer PI, Loretta Barnett RN (University Hospital North Midlands; number of recruits: 63). Total number of recruits: 812.

    • Contributors The study was designed by TMR, who also ran the study data gathering and management of the sample and results. Specialist biochemical and genetic analyses were performed by KT and KB. Data were analysed by TMR and ASW, and they wrote the study manuscript. The final manuscript as submitted was approved by all the authors.

    • Funding This work was supported by an investigator grant from Genzyme Therapeutics, Oxford, which merged with Sanofi to become Sanofi Genzyme after the study commenced. Research nurses were funded by the National Institute for Health Research.

    • Competing interests TMR is currently in receipt of project grants from Genzyme Therapeutics, Oxford, UK (now Sanofi Genzyme, Oxford, UK); Shire Pharmaceuticals, Basingstoke, UK; and Synageva BioPharma, Watford, UK (now Alexion Pharma UK, Uxbridge, UK).

    • Patient consent for publication Not required.

    • Ethics approval The project received ethics approval from the National Research Ethics Service Committee East Midlands - Northampton (UK Integrated Research Application System project number 158121; 14/EM/1153; 14/10/2014). It was included in the National Institute for Health Research portfolio (UKCRN ID: 17588) and transferred to Health Research Authority on 15 June 2016.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data availability statement Data are available upon reasonable request.