Fabry disease - a risk factor for renal cell cancer? - case series

Fabry disease (FD) is an X-linked lysosomal storage disease characterised by glycosphingolipid globotriaosylceramide (Gb3) accumulation in the lysosomes of multiple organs including the kidneys. Anecdotally we observed a higher-than-expected incidence of renal cell carcinoma (RCC) in FD patients.

Retrospective, observational study at two specialist national centres for lysosomal storage disorders (LSD) in the UK and Netherlands looking after a total of 520 patients with FD, 289 with a classical phenotype and 231 with non-classical 'cardiac variant' phenotype.

There were 11/520 (equivalent 70.5/100000/year) incidences in 10 patients with an additional diagnosis of RCC. The median (IQR) age at RCC diagnosis was 55 (39-59) years. 5/10 were identified incidentally. RCC affected 6/289 (2.1 %) patients with classical Fabry disease and 5/231 (2.2 %) with the non-classical phenotype. The median (range) plasma lyso-Gb3 concentration was 21.6 (2.9-95.6 nmol/L). 55 % of RCCs were diagnosed before starting disease modifying treatment, the remaining were diagnosed 5-18 years after the start of treatment. Commonest subtype was clear-cell-RCC (7/11 incidences with 7 patients having WHO/ISUP grade 2 or above tumours. 3 had papillary-RCC (1 had two episodes at age 27 and 39).

The annual incidence of RCC in patients with FD was higher than the peak global incidence (70.5 vs 4.6/100000/year) and occurred at a younger age. FD may be an independent risk factor for RCC. This suggests that routine screening for RCC may be beneficial in patients with FD.

Fabry disease may be an independent risk factor for renal cell carcinoma. What was known: Renal involvement, primarily progressive chronic kidney disease (CKD) is a well-known manifestation of Fabry disease. This study adds: Our findings indicate a significant increase in RCC among patients with FD. Potential impact: Effective screening tool will be available for patient with this genetic condition and further research into the mechanisms by which GLA gene variants increase RCC risk may enhance our understanding of RCC pathophysiology and inform the development of new therapeutic approaches.