PALMITOYL-PROTEIN THIOESTERASE DEFICIENCY IN A NOVEL GRANULAR VARIANTOF LINCL

Typically, late infantile neuronal ceroid-lipofuscinosis (LINCL) patie nts present between the ages of 2 and 4 years with progressive dementi a, blindness, seizures, and motor dysfunction. Curvilinear profiles ar e seen on electron microscopic examination of tissues derived from tho se patients. Data were collected on 122 LINCL cases, representing 81 i ndependent families, diagnosed on the basis of age of onset, clinical symptomatology, and pathologic findings. Careful analysis of our data has revealed that 20% of these cases (24 of 122) show either an atypic al clinical course or atypical pathologic findings and may represent v ariants of LINCL. Recent progress in the biochemistry and molecular ge netics of NCL has led us to reevaluate these atypical cases. Five atyp ical LINCL cases (representing three independent families) manifested granular inclusions when examined by electron microscopy, a finding no rmally associated with the infantile form of NCL. In addition, these f ive cases did not show elevated subunit c levels in urine (typically s een in LINCL). In these five cases, palmitoyl-protein thioesterase act ivity was found to be deficient (less than 10% normal activity), sugge sting that these cases represent INCL, presenting at a later age of on set. These findings suggest that palmitoyl-protein thioesterase defici ency is not restricted to infantile onset cases, and they raise the po ssibility that milder forms of INCL may result from less deleterious m utations. (C) 1998 by Elsevier Science Inc. All rights reserved.