Adult neuronal ceroid lipofuscinosis caused by deficiency in palmitoyl protein thioesterase 1

Abstract

The neuronal ceroid lipofuscinoses (NCLs) are the most common group of neurodegenerative diseases in children. Mutations in the CLN1 gene, which encodes the enzyme palmitoyl protein thioesterase 1 (PPT1), usually cause infantile-onset NCL (INCL) (Santavouri-Haltia disease, MIM 256730).1 INCL has an age at onset of 8 to 18 months with rapid visual and psychomotor deterioration, ataxia, hypotonia, and seizures.2 Retinal pigment aggregation does not usually occur. In all cases, a granular pattern of storage material in cells is observed by electron microscopy. However, in one family, onset was as late as adulthood.3 We describe a second family with adult-onset NCL caused by a novel mutation in the CLN1/PPT1 gene. A 24-year-old woman with no significant family history was diagnosed with hypomanic episodes because of a 12- to 24-month history of “low self-esteem and mood, irritability, lack of interest, and bizarre behavior including a tendency to wander the streets” and thus treated with olanzapine and valproate. A few months later, she reported the inability to see properly. Ophthalmologic evaluation showed normal visual acuity, pupillary reaction, and normal optic discs and macular and retinal appearance in the presence of “extremely tubular” tunnel vision in both eyes when the automated visual field tests were performed but with inconsistent responses on Goldman’s fields assessment. She had a history of declining academic abilities after age 18 years. She was emotionally labile, but no other neurologic abnormalities were detected. Brain MRI showed marked generalized cerebral and cerebellar atrophy with no focal abnormalities (figure) (see also figure E-1 on the Neurology Web site at www.neurology.org). Hematologic, biochemical, and vasculitic screens and standard lysosomal enzymes assays were normal. Visual evoked responses were delayed bilaterally. Flash electroretinograms …