Tags

Type your tag names separated by a space and hit enter

Identification of patients with Pompé disease using routine pathology results: PATHFINDER (creatine kinase) study.

Abstract

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.

Authors+Show Affiliations

Clinical Chemistry, Queen's Hospital, Burton-on-Trent, UK.Willink Biochemical Genetics Unit, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.Willink Biochemical Genetics Unit, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.Metabolic Medicine/Chemical Pathology, Guy's & St Thomas' Hospitals, London, UK anthony.wierzbicki@kcl.ac.uk.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31308256

Citation

Reynolds, Tim M., et al. "Identification of Patients With Pompé Disease Using Routine Pathology Results: PATHFINDER (creatine Kinase) Study." Journal of Clinical Pathology, 2019.
Reynolds TM, Tylee K, Booth K, et al. Identification of patients with Pompé disease using routine pathology results: PATHFINDER (creatine kinase) study. J Clin Pathol. 2019.
Reynolds, T. M., Tylee, K., Booth, K., & Wierzbicki, A. S. (2019). Identification of patients with Pompé disease using routine pathology results: PATHFINDER (creatine kinase) study. Journal of Clinical Pathology, doi:10.1136/jclinpath-2019-205711.
Reynolds TM, et al. Identification of Patients With Pompé Disease Using Routine Pathology Results: PATHFINDER (creatine Kinase) Study. J Clin Pathol. 2019 Jul 15; PubMed PMID: 31308256.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Identification of patients with Pompé disease using routine pathology results: PATHFINDER (creatine kinase) study. AU - Reynolds,Tim M, AU - Tylee,Karen, AU - Booth,Kathryn, AU - Wierzbicki,Anthony S, AU - ,, AU - ,, Y1 - 2019/07/15/ PY - 2019/01/07/received PY - 2019/06/09/revised PY - 2019/06/20/accepted PY - 2019/7/17/entrez KW - alpha 1,4 glucosidase KW - creatine kinase, screening KW - fabry disease KW - glycogen storage disease KW - lysosomal acid maltase KW - pompé disease JF - Journal of clinical pathology JO - J. Clin. Pathol. N2 - 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. SN - 1472-4146 UR - https://www.unboundmedicine.com/medline/citation/31308256/Identification_of_patients_with_Pompé_disease_using_routine_pathology_results:_PATHFINDER_(creatine_kinase)_study L2 - http://jcp.bmj.com/cgi/pmidlookup?view=long&amp;pmid=31308256 DB - PRIME DP - Unbound Medicine ER -