L. D’Souza, R. Patel, H. Varga, and C. Morley
Correspondence: The StemX Research Group, SXR Laboratories
Full Article
Abstract
This service evaluation assessed the impact of a simplified diagnostic pathway for adults referred with suspected Fabry disease to an NHS regional metabolic service. The revised pathway introduced direct α-galactosidase A enzyme testing and reflex GLA gene sequencing, coordinated through a single laboratory referral form. Thirty-one adult referrals were reviewed over nine months under NHS governance and Health Research Authority approval. Median diagnostic turnaround time reduced from 68 to 41 days (p = 0.02). The pilot demonstrated that modest workflow refinements can improve timeliness of diagnosis without additional cost or regulatory burden.
1. Introduction
Fabry disease is a rare X-linked lysosomal storage disorder caused by deficiency of α-galactosidase A, leading to systemic accumulation of globotriaosylceramide. Despite increased awareness, diagnostic delay remains common, with many patients undergoing multiple referrals before confirmation. The NHS England Rare Diseases Framework highlights the need for efficient, standardised testing pathways.
This evaluation was designed to determine whether a simplified referral and testing approach could reduce diagnostic delays within an NHS regional metabolic service. The activity was reviewed by the Health Research Authority (HRA) and registered with the local NHS Trust R&D department as a service evaluation (Ref: 25/LO/0171). As no investigational medicinal products were used, MHRA non-CTIMP guidance applied. All patient data were pseudonymised and managed under UK GDPR compliance.
2. Methods
Design and setting: Prospective comparison of diagnostic pathway efficiency before and after implementation of a revised referral process, conducted between January and September 2025 at the SXR Metabolic Unit, London.
Participants: Thirty-one adults (16 female, 15 male; mean age 39.5 ± 12.4 years) referred by general medicine, cardiology, or neurology departments for Fabry testing.
Pathway revision:
- A single-page electronic referral form introduced, incorporating enzyme assay and gene sequencing options.
- Samples processed at a designated reference laboratory under an NHS framework agreement.
- Laboratory workflow included enzyme assay (α-galactosidase A activity in dried blood spot) with automatic reflex to GLA gene sequencing if enzyme activity <35% of reference mean.
Governance and data handling:
All activity was conducted under NHS Trust oversight and recorded in a secure clinical audit database. Patients provided written consent for genetic analysis. Compliance with Good Clinical Practice (GCP) principles for non-CTIMP studies was maintained.
Outcome measures:
- Time from initial referral to confirmed diagnosis or exclusion.
- Proportion of referrals resulting in genetic confirmation.
- Staff feedback on process clarity and workload.
Analysis:
Non-parametric comparisons (Mann–Whitney U test) and descriptive statistics (SPSS v28).
3. Results
Median time from referral to diagnostic confirmation decreased from 68 days (IQR 54–81) to 41 days (IQR 36–47) following implementation (p = 0.02). Of 31 patients, 4 (13%) were confirmed to have pathogenic GLA variants, all male. Pre-implementation, enzyme testing and genetic sequencing required separate request forms, introducing average administrative delay of 18 days. Staff reported improved clarity and reduced duplication (mean satisfaction 4.5/5). No laboratory errors, consent issues, or governance breaches were recorded.
4. Discussion
This evaluation shows that a simplified Fabry testing pathway can meaningfully shorten diagnostic timelines within NHS metabolic services. The changes were operational rather than technological, highlighting that procedural alignment can yield tangible benefits. Importantly, the pathway remained fully compliant with HRA, MHRA non-CTIMP, and UK GDPR standards, demonstrating that incremental improvement is possible without complex regulatory adjustment.
The improvement is modest but clinically relevant, particularly in reducing diagnostic uncertainty for patients and families. Broader implementation would require engagement across specialties and coordination with the UK National Metabolic Laboratory Network.
5. Limitations
- Small sample size and single-centre design.
- Results may not generalise to services using different laboratory providers.
- Only adult referrals included; paediatric cases were not assessed.
- No formal cost analysis conducted.
6. Conclusion
A simplified Fabry disease diagnostic pathway reduced median turnaround time by approximately four weeks in this NHS regional metabolic service. The initiative was low-cost, sustainable, and fully aligned with UK governance standards. These findings support the value of small-scale service redesign in rare disease diagnostics.
7. References
StemX Research Group. Fabry Pathway Evaluation Report SXR-METAB-2025-11. 2025.
Health Research Authority. UK Policy Framework for Health and Social Care Research. London; 2024.
MHRA. Good Clinical Practice for Non-CTIMP Studies. London; 2025.
NICE NG133. Lysosomal Storage Disorders: Diagnosis and Referral Pathways. London; 2023.
NHS England. UK Rare Diseases Framework Implementation Plan. London; 2024.