LETTER TO THE EDITOR Identification of a patient affected by ‘‘Juvenile-chronic’’ Tay Sachs disease in South Italy M. Liguori 1 • G. Tagarelli 2 • N. Romeo 2 • A. Bagala ` 2 • Patrizia Spadafora 2 Received: 22 December 2015 / Accepted: 22 June 2016 Ó Springer-Verlag Italia 2016 Keywords Tay Sachs Á Hexa gene Á TSD Á Juvenile-chronic onset Á Ataxia Á Psychosis Dear Editor, Tay Sachs disease (TSD) is an autosomal recessive neu- rodegenerative disorder characterized by lysosomal enzyme b-hexosaminidase A (HexA) deficiency resulting in GM2 ganglioside accumulation mainly in neurons. To date 130 mutations have been reported in the HEXA gene (15q23-q24) that encodes for the a-subunit of b-hex- osaminidase A; they are private or common in some ethnic groups and geographic isolates. Typically, TSD starts in the infancy with psychomotor retardation, blindness and seizures. Death occurs within few years. Late onset TSD is divided into subacute ‘‘juvenile’’ and chronic ‘‘adult’’ forms. Juvenile TSD exhibits spasticity, seizures, blindness and dementia progressing into a vegetative state (5–15 years). Adult TSD shows signs of cerebellar involvement like dysmetria, ataxia, tremor; psychosis and mood disturbances can be the starting features [1]. Here, we describe a 30-year-old woman from an isolated village of Calabria (South Italy) with early-onset depres- sion and cerebellar ataxia. Her healthy parents were sec- ond-degree cousins (Fig. 1a). The proband showed a severe bipolar depression at around age 9 years for which she was treated with neuroleptic drugs (e.g., phenothiazine) without benefit; at the age of 17 she was hospitalized for halluci- nations. At 19 years old, she developed a progressive gait instability that led to severe walking impairment so she was no longer able to walk without assistance at the age of 25. When we first examined her, she showed severe ataxia, tremor, dysphagia, dysarthria, but no cognitive decline (MMSE 28/30); her bilateral visual acuity resulted normal. No clinical signs of muscular weakness were detected; the electrophysiological exam (EMG) of nerve conductions (motor and sensitive, lower and upper limbs) was normal. Brain magnetic resonance imaging revealed severe cere- bellar atrophy (T2-weighted sequences). Genetic tests excluded recessive spinocerebellar ataxias, whereas b- hexosaminidase A activity determination showed a very low value ( \ 10 %) suggesting a diagnosis of TSD. After informed consent, the genomic DNA analysis of the HEXA gene was performed by ABI3130XL Genetic Ana- lyzer. In the proband (III-3), a Gly269Ser mutation in com- pound heterozygosity with Leu127Arg was found. Her father (II-l) and mother (II-2) were heterozygous for Gly269Ser and Leu127Arg alleles, respectively. The proband’s sister (III-2) was heterozygous for Gly269Ser (Fig. 1a, b). Several late onset TSD cases have been reported; among them, all Ashkenazi-Jewish were compound heterozygotes for the Gly269Ser change and one of the infantile-TSD mutations. In contrast, non-Jewish patients were more often homozygous for this mutation [1]. In this case report, the TSD patient carrying both the Gly269Ser and the Leu127Arg mutations originated from South Italy. To the best of our knowledge, the first muta- tion was never reported in Italy, whereas Leu127Arg has been identified in two Italian children with acute infantile TSD [2]. In our view, the clinical phenotype of our patient is quite unusual: psychiatric symptoms have been often described & Patrizia Spadafora patrizia.spadafora@cnr.it 1 Institute of Biomedical Technologies, National Research Council, Section of Bari, Bari, Italy 2 Institute of Neurological Sciences, National Research Council, c/da Burga, 87050 Piano Lago di Mangone, CS, Italy 123 Neurol Sci DOI 10.1007/s10072-016-2646-2