The prevalence of the IL-6 C allele significantly influences MSSI, i.e. clinical severity, especially in females. This is unrelated to IL-6 as a pro-inflammatory marker as demonstrated by lack of correlations with CRP levels and genotypes. IL-6 -174 polymorphic C allele may be a prognostic marker in Fabry disease, especially in females.

Both men and women with Fabry disease are affected by hearing impairment. It seems that the hearing loss is less marked in female than in male patients. Children with Fabry disease complain of tinnitus more frequently than other children and quite early in the course of the disease.

Background: Fabry disease is associated with cardiomyopathy, early-onset stroke, and progressive renal failure, and other features. No markers predict multisystemic disease progression. The hypothesis of the current study is to assess a clinically relevant marker for Fabry disease using polymorphic genotyping of a marker that has been shown to be involved in interrelated cardiac, vascular, and renal abnormalities in patients not affected by Fabry disease. The paraoxonase (PON1) polymorphisms, Leu55Met and Gln192Arg, modulate intima-medial artery thickening, prognosis of cardiovascular stroke, and renal failure in other diseases. Methods: PON1 polymorphisms were ascertained. The Mainz Severity Score Index (MSSI) for Fabry disease was calculated. Local Institutional Review Board approval was received. Results: 104 patients (58 female) and 46 controls (23 female) were evaluated. There was a significant difference (p = 0.04) in PON55LL (42.3%) among patients as compared to controls (21.7%) but none in PON192 genotypes. PON55 variant (MM) was correlated with severe MSSI renal sub-scores (p < 0.001) also when age-adjusted but not with cardiac, neurological, or general sub-scores. PON55LL genotype, correlated with higher PON1 activity, had lowest α-galactosidase-A activity (n = 45). Conclusion: There was no combined effect of PON55-PON192 polymorphisms. PON55LL was more common among patients. PON55MM genotype was correlated with non-mild renal sub-scores. However, sample size needs to be enlarged.