The spectrum of neurological manifestations of Fabry disease in alarge Turkish family with c.[680G>A] p.[R227Q]mutation
- Author:
Aslı Aksoy Gündog˘du
;
Zeynep Özözen Ayas
;
Murat Alemdar
;
DilcanKotan
- Publication Type:Original article
- Keywords:
Fabry Disease;
GLA mutation;
family screening;
pedigree
- MeSH:
Fabry Disease
- From:Neurology Asia
2017;22(3):253-259
- CountryMalaysia
- Language:English
-
Abstract:
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.
