The aim of the study was to determine the clinical features and molecular genetic patterns of patients with Fabry disease (FD) to optimize the diagnostic stepwise.
Object and methods. The comparison of clinical features was performed and the activity of lysosomal enzyme a–galactosidase A in the peripheral blood leukocyte homogenate was studied in 120 male with the neuropathic pain or acroparesthesia who contacted the Center of Orphan Diseases of NSCH “Ohmatdyt” in years 2002–2016. The cascade family screening (in 8 people) at low enzyme levels and molecular genetic analysis for the presence of mutations in the GLA gene were performed.
Results. The activity of –galactosidase A was decreased (range 0.5–12.6 nM/mg/h with median 2.0 nM/mg/h) in nine cases (7.5%). All these patients had additional clinical signs (angiokeratoma, hypertrophic cardiomyopathy, coarse facial features, and compromised family tree). The diagnosis of FD were confirmed by the molecular genetic analysis in the GLA gene; there were identified two new mutations (p.739 740delAA and C.945 946delinsTTGA). The other mutations in 6 out of 8 examined families were revealed by the screening of the first kinship degree female relatives, but the activity of –galactosidase A in leukocytes was only reduced in 4 of them.
Conclusion. The multisystem lesions and the difference in the clinical signs of FD complicate the timely formulation of diagnosis. Selective screening among patients with renal insufficiency, cardiac pathology, and ischemic stroke in the anamnesis increases the possibility of FD diagnosis. Cascade family screening of FD patients relatives is highly effective in identification new patients with non–classical form of FD. Inclusion in the selective group of persons with chronic diseases, compromised pedigree, acroparesthesia and additional FD probable clinical signs reduces the range ofpatients for further high–cost testing and optimizes the diagnosis of FD.
Clinical features and molecular genetic analysis
in a Turkish family with oral white sponge nevus