Vol 12, No 3 (2017)

Fabry disease (Anderson–Fabry disease) is an X-linked recessive lysosomal storage disorder resulting from deficient activity of lysosomal hydrolase, alpha-galactosidase A, which leads to progressive accumulation of globotriaosylceramide (Gb3) in various cells (predominantly endothelial and vascular smooth muscle cells) with clinical manifestations affecting major organs including the central nervous system. Clinical onset of Fabry disease usually occurs in childhood, but many patients are diagnosed in adulthood. Early recognition of symptoms, enzyme activity levels, concentration of Gb3 in the blood, urine and skin bioptates, as well as genetic testing (GLA gene) enable establishment of early diagnosis and therapeutic intervention with enzyme replacement therapy. Early therapy may prevent complications of the disease.

The Aristaless-related homeobox (ARX) gene is a member of the paired-type homeodomain transcription factor family with critical roles in embryonic development, particularly in the developing brain. Mutations in ARX gene demonstrate striking intra- and interfamilial pleiotropy together with genetic heterogeneity and lead to a broad spectrum of diseases. They give rise to 4 key phenotypic features: a different types of brain malformation, abnormal genitalia, epilepsy and intellectual disability. Authors present 3 clinical cases: a girl with duplication on the short arm of X-chromosome (Xp11.22-p22.33), which include genes ARX and CDKL5; a girl and a boy with a missense mutation in ARX gene that have not been previously described (chrX:25031522C>A), causes the substitution of an amino acid in the 197 protein position (p.Gly197Val, NM_139058.2). All patients suffer from severe epilepsy, that is refractory to antiepileptic drugs, and all of them have different degrees of psychomotor delay. The patients with missense mutation also have movement disorders: stereotypic movements in the girl and choreo athetosis and dystonia in the boy. Electroencephalographic abnormalities have been identified in all patients, and there were not significant abnormalities on magnetic resonance imaging in all cases. The described cases broaden the clinical spectrum of mutations in ARX gene.

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