Background: Fabry disease (FD, OMIM #301500) is a rare, progressive, X-linked, inherited genetic disease caused by a functional deficiency of lysosomal α-galactosidase, leading to the accumulation of glycosphingolipids in virtually all of the body’s cell types and fluids. Patients with rare genetic diseases and non-specific symptoms often experience substantial diagnostic delays, which can negatively impact the prompt initiation of treatment. If FD is not treated specifically, end organ damage (such as chronic renal failure, hypertrophic cardiomyopathy with arrhythmia, and strokes) impairs quality of life and reduces life expectancy. Patients and Methods: For 83 consecutive patients with FD referred to the Russian reference center for lysosomal storage diseases, family trees were built and genetic testing (cascade genotyping) was offered to family members. Results: The pathogenic GLA variant associated with FD was identified for all 83 probands. Family testing using cascade genotyping enabled the identification of 165 additional cases of FD among the tested 331 at-risk family members. Discussion: This is the first study to have described family screening in a large Russian cohort of patients with FD and chronic kidney disease. Raising awareness of FD among clinicians is important for earlier diagnosis and specific treatment.

Heat shock proteins play an important role in immune inflammation and the formation and restoration of proteins. In recent years, the importance of heat shock protein 90 (Hsp90) in the activation of immune inflammation through nuclear factor kB (NFkB) has been discussed. To assess the activation of the Hsp90-NFkB system by measuring serum and urinary levels in patients with chronic glomerulonephritis (CGN). This study included 32 patients with active forms of CGN and 14 patients with Fabry nephropathy. The control group included 10 healthy individuals. Twenty-one out of 32 CGN patients had nephrotic syndrome (NS). Eleven out of 32 CGN patients had proteinuria levels from 1 to 3 g/day without nephrotic syndrome. A total of 17 patients had renal dysfunction (estimated glomerular filtration rate < 60 ml/min/1.73m²). Fourteen patients with Fabry nephropathy had proteinuria without nephrotic syndrome. Serum and urine HSP-90 and NFkB p65 levels were determined using an enzyme-linked immunosorbent assay. The levels of HSP-90 and NFkB in the serum of patients with CGN were significantly higher than in healthy individuals and patients with Fabry nephropathy. In patients with Fabry nephropathy, the HSP-90 and NFkB levels in the urine and serum did not significantly differ from those in the control subjects. Serum Hsp90 levels were significantly higher in the CGN patients with NS than in patients without NS, as well as in patients with normal renal function compared with patients with an eGFR < 60 ml/min/1.73 m² and patients with tubulo-interstitial fibrosis. Higher levels of HSP-90 and NFkB in serum were observed in patients with nephrotic forms of CGN, including focal segmental glomerulosclerosis, minimal change disease and membranous nephropathy. There were no correlations between the clinical signs of CGN and urinary HSP90/NFkB levels. Activation of the HSP-90-NFkB system, which is directly involved in the development of immune inflammation in CGN, was found in patients with an active course of CGN, especially in those with nephrotic syndrome.

Cornea verticillata is the typical sign of ocular involvement in Fabry disease and manifests by the whorl-like, linear opacities in the inferior part of the cornea. Aim. To study the frequency of cornea verticillata in patients with Fabry disease and it’s relation to the severity of the disease and the types of mutation in the GLA gene. Materials and methods. We studied 69 adult (over 18 years) patients with a classic form of Fabry disease that was confirmed by enzymatic and molecular genetic studies. There were 39 males and 30 females. The median age was 39 years [30.0; 50.0]. The severity of Fabry disease was assessed using the Mainz Severity Score Index (MSSI) with a maximum value of 76 points. Depending on the MSSI score, patients were classified into mild (40) clinical categories. Results and discussion. At least one classic symptom of Fabry disease was present in 88.4% of patients. The majority of patients had the missense mutations of the GLA gene. Cornea verticillata was found in 65.2% of patients and occurred with a similar frequency in males (56.4%) and females (76.7%; p=0.07). Cornea verticillata was the single classic symptom of Fabry disease in only 4.9% of cases, while the rest of the patients presented with angiokeratoma, neuropathic pain and/or hypohidrosis. The frequency of classic symptoms of Fabry disease, as well as renal disease (with the exception of terminal chronic renal failure), brain and heart damage was similar in patients with and without cornea verticillata. Median MSSI scores were also similar in patienths with and without cornea verticillata (20.0 and 18.5 points, respectively; p=0.92). Similar results were obtained in males (26.5 and 30.0 points, p=0.97) and females (16.0 and 16.0 points, p=0.45). The frequency of cornea verticillata did not differ in patients with different types of mutations in the GLA gene. Conclusion. Cornea verticillata occured in 65% of adult patients with Fabry disease, was usually accompanied by the other classic symptoms of the disease, and was not associated with the severity of the disease. Keywords: Fabry disease, cornea verticillata, MSSI index