LETTER TO THE EDITOR A case of atypical early-onset Alzheimer’s disease carrying the missense mutation Thr354Ile in exon 10 of the PSEN1 gene Sandro Marini • Giulia Lucidi • Andrea Tedde • Valentina Bessi • Benedetta Nacmias Received: 26 September 2012 / Accepted: 23 November 2012 / Published online: 2 December 2012 Ó Springer-Verlag Italia 2012 To the Editor-in-Chief: We report the presenilin 1 (PSEN1) Thr354Ile mutation in an Alzheimer’s disease (AD) patient with uncommon clinical features. Although the mutation has already been reported [1], only one phenotypic description could be found in literature [2]. Our patient is a 59-year-old women and she worked as a piano teacher in the conservatory and as a concert performer. She was born in Uruguay and was adopted when she was just a few months old; no infor- mation on the biological family was available. She was referred to our neurology unit for a 6-month-history of progressive cognitive and behavioral impairment. Memory difficulties, progressive spatial and temporal disorientation, language disturbances and severe anxiety and agitation were described. No other pathologies are known except of a history of mood depression and few episodes of unmo- tivated jealousy, excessive concern for familial finances. Two months before our visit, a sudden worsening in behavior surfaced: the patient became aggressive, confab- ulating and sleepless. After a brief hospitalization in the psychiatric department, any psychiatric origin of the dis- order was ruled out. Neurological examination revealed good awareness with severe agitation and grave wandering, along with disorientation in space, time and towards peo- ple, confabulating with fluent non-informative speech and poor comprehension. Her face was expressionless and small, shuffling steps were observed, with stationary arms. A neuropsychological examination was not possible to administer due to the severe cognitive impairment. Neu- roleptics were administered, improving the insomnia and psychomotor agitation. Five months after our evaluation, the patient required all-day nursing and was completely dependent. Severe weight loss (12 kg in 5 months) and urinary and fecal incontinence occurred. Three episodes of forward fall, with facial trauma were reported. Characteristic behavior was described: she undressed and dressed herself suddenly several times during the day without any apparent reason. Examination revealed a non-fluent speech with neologism and paraphasia. Only slight comprehension was preserved. Wandering continued unchanged. Primitive subcortical reflexes, right hand motor automatisms and severe ante- rocollis appeared (palpable tonic spasm of the sternomas- toid and posterior neck muscles). The results of the routine laboratory and cerebrospinal fluid (CSF) analysis were normal. Infectious and tumoral diseases were ruled out. Electroencephalography, magnetic resonance imaging of the brain were normal but the positron emission tomography scanning with the fluorodeoxyglucose (18FDG-PET) showed a bilateral hypometabolism in the parietotemporal cortex, the usual findings seen in AD. The CSF levels of Ab42, total-tau, phospho-tau supported the AD diagnosis [3]. The clinical course, especially the relatively early-onset (58 years) and rapid course of dete- rioration suggested the study of the genetics of familial AD. Informed written consent was obtained. Genetic test- ing revealed the missense mutation Thr354Ile in exon 10 of the PSEN1 gene and an apolipoprotein E (APOE) e3/e3 genotype. Mutations in the PSEN1 gene are the most fre- quent cause of familial AD cases [4]. This genomic mutation has been reported previously [1], but without accompanying clinical information, and, to date, epidemi- ological data, such as age of onset, clinical spectrum and S. Marini Á G. Lucidi Á A. Tedde Á V. Bessi Á B. Nacmias (&) Department of Neurological and Psychiatric Sciences, University of Florence and Centro di Ricerca, Trasferimento e Alta Formazione DENOTHE, University of Florence, Largo Brambilla, 3, 50134 Florence, Italy e-mail: nacmias@unifi.it 123 Neurol Sci (2013) 34:1691–1692 DOI 10.1007/s10072-012-1260-1