Clinical picture of a patient with a novel PSEN1 mutation (L424V)

Abstract

Young onset dementia raises concern about familial and non degenerative dementias. We describe a patient with early dementia. At the age of 26, a woman developed symptoms of anorexia nervosa, at 30 a memory and attention deficit, and at 34 abnormal behavior with impulsivity, aggression, and dysexecutive disorder. At 36 she showed aphasia, stereotyped behavior, hyperreflexia, grasping reflex, urinary incontinence, myoclonus, and seizures. Blood and cerebrospinal fluid were normal. Brain computed tomography and single photon emission computed tomography showed diffuse cortico-subcortical atrophy and frontotemporoparietal hypoperfusion. A Leu424Val mutation was present in PSEN1 gene. PSEN1 mutations can produce Alzheimer's disease, frontotemporal dementia, and dementia with Lewy bodies phenotypes, or a combination of them. It has been proposed that the mutation type and location may influence the molecular pathogenesis and thus PSEN1 would represent a molecular connexion between these entities. This case shows a novel PSEN1 mutation with outstanding amnesic and frontal symptoms.