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Identification of patients with Fabry disease using routine pathology results: PATHFINDER (eGFR) study
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  • Tim Reynolds,
  • Karen Tylee,
  • Kathryn Booth,
  • Anthony Wierzbicki
Tim Reynolds
Burton Hospitals NHS Foundation Trust
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Karen Tylee
Manchester University NHS Foundation Trust
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Kathryn Booth
Manchester University NHS Foundation Trust
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Anthony Wierzbicki
Guy's and Saint Thomas' NHS Foundation Trust
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Aims: Lysosomal α-galactosidase A deficiency (Fabry disease (FD)) was considered an X-linked recessive disorder but is now viewed as a variable penetrance dominant trait. The prevalence of FD is 1 in 40000-117,000 but the exact frequency is disputed depending on ascertainment of late-onset cases and degree of female penetrance. Its prevalence in the general population, especially in patients with abnormal renal function is unclear. This study attempted to identify the prevalence of FD in patients with abnormal results identified from laboratory databases. Methods: Electronic laboratory databases were interrogated to identify from clinical biochemistry records patients with a phenotype of reduced estimated glomerular filtration rate categorised by age on one occasion or more over a 3-year time interval. Patients were recalled and a dried blood spot sample was collected for determination of α-galactosidase A activity by fluorimetric enzyme assay in men and mass spectrometry assays of α-galactosidase A and lyso-globotriaosylceramide (lyso-GL-3) concentrations in women. Results: Samples were obtained from 1084 patients identified with reduced renal function. No cases of FD were identified in 505 men. From 579 women one subject with reduced α-galactosidase activity (1.5 µmol/l/hr) and increased Lyso-GL-3 (5.5 ng/ml) was identified and shown to be heterozygous for a FD mutation (c.898C>T; p.L300F; Leu300Phe). It was later confirmed she was a relative of a known affected patient. Conclusions: Pathology databases hold routine information that can be used to identify patients with inherited errors of metabolism. Biochemical screening using reduced eGFR has a low yield for unidentified cases of Fabry Disease.

Peer review status:Published

30 May 2020Submitted to International Journal of Clinical Practice
10 Jun 2020Submission Checks Completed
10 Jun 2020Assigned to Editor
12 Jun 2020Reviewer(s) Assigned
22 Jun 2020Review(s) Completed, Editorial Evaluation Pending
15 Jul 20201st Revision Received
16 Jul 2020Submission Checks Completed
16 Jul 2020Assigned to Editor
16 Jul 2020Reviewer(s) Assigned
04 Aug 2020Review(s) Completed, Editorial Evaluation Pending
06 Aug 2020Editorial Decision: Accept
10 Aug 2020Published in International Journal of Clinical Practice. 10.1111/ijcp.13672