Tay Sachs in South Italy

Tay Sachs disease (TSD) is an autosomal recessive neurological disorder characterized by significant deficiency of lysosomal enzyme ?-Hexosaminidase A and subsequent intralysosomal accumulation of GM2 ganglioside. Tay Sachs disease has been extensively studied in the Ashkenazy Jewish population because of an elevated incidence of cases.We have described in a recent work a young woman of 30 years old with early onset depression at around age 9, inbalance with tendency to fall and cerebellar ataxia developed at 19 years old. She was no longer able to walk without assistance at age of 25. This patient originated from an isolated village of Calabria, South Italy. Genetic tests excluded recessive spinocerebellar ataxias. In vitro determination of the ?-Hexosaminidase A activity showed a low value (< 10%) suggesting a diagnosis of TSD. Direct sequencing of HEXA gene revealed Gly269Ser mutation in compound heterozygosity with Leu127Arg. The identification of two different mutations in HEXA gene in the young woman reported by us originating from an isolated village of southern Italy, and the finding of consanguinity in the family (proband's parents were second-degree cousins), suggested the presence in this country of a founder effect of Ashkenazi Jews origin. In support of this hypothesis, historical sources indicated the presence of Jews in Calabria since eleventh century.