Fabry Disease: Screening and Analysis of the Associated Clinical Manifestations in Patients Attending Dialysis and Nephrology Clinics in Durban, South Africa

Abstract

Abstract Background Fabry disease is inherited in an X-linked manner in which the mutated gene inhibits the functioning of the alpha-Galactosidase-A enzyme causing a deficiency or absence of the enzyme, characterising it as a progressive, lysosomal storage disorder. Subsequently, the accumulation of globotriaosylceramide (Gb3) in the lysosomes causes damage to tissues and major organs. Fabry nephropathy is one of the major organ complications caused by Fabry disease resulting in end-stage kidney disease. To our knowledge, no research has been conducted to determine the association between Fabry disease, its clinical manifestations, and chronic kidney disease in Durban. Methods This study was a prospective, quantitative study. A cohort of 200 male patients with chronic kidney disease (CKD stage 2-5D) was enrolled. A control group of 14 healthy males was also enrolled for this study. The ELISA technique was employed to determine the alpha Gal-A enzyme concentration levels in plasma. A questionnaire using the MSSI scoring system was presented to the participants to identify clinical manifestations. The SPSS Version 27 (IBM, New York, USA) was used to analyse the data. Results A cut-off value for the alpha Gal-A enzyme concentration levels of < 500pg/ml was calculated. A total of 17 participants from the patient group (n = 11) and the control group (n = 6) displayed alpha-Gal-A enzyme levels < 500pg/ml. The univariate regression analysis revealed, statistically significant association between alpha-Gal levels < 500pg/ml and age (p = 0.007), heat or cold intolerance (p = 0.049), hypertension (p < 0.001) and eGFR (p < 0.001). MSSI scores displayed a negative association (p = 0.001). The multivariate regression analysis showed that age and MSSI scores retained their significance when eGFR was excluded as a variable, however, with the inclusion of eGFR as a variable, none of the variables retained their significance. Conclusion Fabry disease is suspected in 17 participants with alpha-Gal levels of < 500pg/ml. The cause of CKD nephropathy raises interest as conditions such as FSGS have been associated with FD. The low levels of the alpha-Gal enzyme and the presentation of the clinical manifestations can be utilised as preliminary findings. Confirmatory tests such as DNA analysis or Gb3 and GL3 analysis should be performed to confirm the diagnosis.