Palmitoyl-protein thioesterase deficiency in a novel granular variant of LINCL

Krystyna E. Wisniewski, Fred Connell, Wojciech Kaczmarski, Aleksandra Kaczmarski, Aristotle Siakotos, Carlos R. Becerra, Sandra L. Hofmann

Research output: Contribution to journalArticle

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Abstract

Typically, late infantile neuronal ceroid-lipofuscinosis (LINCL) patients present between the ages of 2 and 4 years with progressive dementia, blindness, seizures, and motor dysfunction. Curvilinear profiles are seen on electron microscopic examination of tissues derived from those patients. Data were collected on 122 LINCL cases, representing 81 independent 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 atypical clinical course or atypical pathologic findings and may represent variants of LINCL. Recent progress in the biochemistry and molecular genetics of NCL has led us to reevaluate these atypical cases. Five atypical LINCL cases (representing three independent families) manifested granular inclusions when examined by electron microscopy, a finding normally associated with the infantile form of NCL. In addition, these five cases did not show elevated subunit c levels in urine (typically seen in LINCL). In these five cases, palmitoyl-protein thioesterase activity was found to be deficient (less than 10% normal activity), suggesting that these cases represent INCL, presenting at a later age of onset. These findings Current Therapy and New Perspectives in the Treatment of Medulloblastoma suggest that palmitoyl-protein thioesterase deficiency is not restricted to infantile onset cases, and they raise the possibility that milder forms of INCL may result from less deleterious mutations.

Original languageEnglish (US)
Pages (from-to)119-123
Number of pages5
JournalPediatric Neurology
Volume18
Issue number2
DOIs
StatePublished - Feb 1998

Fingerprint

Neuronal Ceroid-Lipofuscinoses
Protein Deficiency
Age of Onset
Medulloblastoma
Blindness
Biochemistry
Dementia
Molecular Biology
Electron Microscopy
Seizures
Urine
Electrons
Mutation
palmitoyl-protein thioesterase
Ceroid Lipofuscinosis, Neuronal, 6
Therapeutics

ASJC Scopus subject areas

  • Clinical Neurology
  • Pediatrics, Perinatology, and Child Health
  • Developmental Neuroscience
  • Neurology

Cite this

Wisniewski, K. E., Connell, F., Kaczmarski, W., Kaczmarski, A., Siakotos, A., Becerra, C. R., & Hofmann, S. L. (1998). Palmitoyl-protein thioesterase deficiency in a novel granular variant of LINCL. Pediatric Neurology, 18(2), 119-123. https://doi.org/10.1016/S0887-8994(97)00173-2

Palmitoyl-protein thioesterase deficiency in a novel granular variant of LINCL. / Wisniewski, Krystyna E.; Connell, Fred; Kaczmarski, Wojciech; Kaczmarski, Aleksandra; Siakotos, Aristotle; Becerra, Carlos R.; Hofmann, Sandra L.

In: Pediatric Neurology, Vol. 18, No. 2, 02.1998, p. 119-123.

Research output: Contribution to journalArticle

Wisniewski, KE, Connell, F, Kaczmarski, W, Kaczmarski, A, Siakotos, A, Becerra, CR & Hofmann, SL 1998, 'Palmitoyl-protein thioesterase deficiency in a novel granular variant of LINCL', Pediatric Neurology, vol. 18, no. 2, pp. 119-123. https://doi.org/10.1016/S0887-8994(97)00173-2
Wisniewski KE, Connell F, Kaczmarski W, Kaczmarski A, Siakotos A, Becerra CR et al. Palmitoyl-protein thioesterase deficiency in a novel granular variant of LINCL. Pediatric Neurology. 1998 Feb;18(2):119-123. https://doi.org/10.1016/S0887-8994(97)00173-2
Wisniewski, Krystyna E. ; Connell, Fred ; Kaczmarski, Wojciech ; Kaczmarski, Aleksandra ; Siakotos, Aristotle ; Becerra, Carlos R. ; Hofmann, Sandra L. / Palmitoyl-protein thioesterase deficiency in a novel granular variant of LINCL. In: Pediatric Neurology. 1998 ; Vol. 18, No. 2. pp. 119-123.
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