Background& Objectives: Fabry disease (FD) is a rare lysosomal storage disease with X-linked recessive inheritance caused by a mutation in the α-galactosidase A gene (GLA) (X14448.1) on chromosome X, leading to α-galactosidase (α-Gal A) (EC: 3.2.1.22) enzyme deficiency. In this report, we present the genetic mutations, clinical features and the neurological involvement of a large Turkish family with FD diagnosed in our clinic during the etiological investigation of a young index patient with recurrent ischemic stroke episodes. Methods: We evaluated 20 members (9 male, 11 female) of a large Turkish family including the index patient. All of them were investigated with a detailed medical history, systemic and neurological examination. Enzyme activity of α-Gal A and GLA gene mutation were tested using dried blood spot (DBS) method. The normative value of α-Gal A enzyme activity was above the cut-off value of 1.2 μmol/l/h. Results: The α-Gal A activity was low in 13 cases (5 male, 27.7%). A total of 13 patients (4 male patients out of 5 males with low enzyme activity and 9 female patients) were found to have a c.[680G>A] p.[R227Q] missense mutation in the GLA gene. Ischemic stroke, renal disorder, cardiomyopathy, neuropathic pain, acroparesthesia, hearing loss, ocular involvement, angiokeratoma, hypohydrosis and hyperhydrosis were the clinical manifestations of FD in the affected family members. Conclusion: The clinical and genetic features of this large Turkish family with FD support an association between the neurological phenotype and the c.[680G>A] p.[R227Q] mutation. Since FD is treatable, it is recommended to perform enzymatic and genetic studies among family members.
Fabry Disease