Infantile neuronal ceroid lipofuscinosis: No longer just a 'Finnish' disease

S. L. Hofmann, A. K. Das, J. Y. Lu, K. E. Wisniewski, Praveena Gupta

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The neuronal ceroid lipofuscinoses (NCLs) are a group of enigmatic neurodegenerative disorders of children that have in common the storage of autofluorescent lipofuscin, or aging pigment, in the brain. With the identification of the three major genes involved in the disorder, the NCLs are now appreciated to represent true lysosomal storage disorders. The most severe (infantile) form of NCL is caused by mutations in a lysosomal thioesterase that removes fatty acids from modified cysteine residues in proteins. Although the disorder was first described in Finland (and the identification of the underlying gene (CLN1) made in this population) defects in CLN1 and the underlying deficiency have been widely reported outside of Scandinavia. In this report, we summarize the relationship of genotype to phenotype in the disorder and evaluate known mutations in light of the recently solved crystal structure of defective enzyme, palmitoyl-protein thioesterase (PPT). We also discuss progress in identifying the fatty acyl cysteine thioesters that accumulate in PPT deficiency and in working toward animal models of NCL. Recent progress in these areas holds promise for the eventual treatment of the disorder.

Original languageEnglish (US)
Pages (from-to)47-51
Number of pages5
JournalEuropean Journal of Paediatric Neurology
Volume5
Issue numberSUPPL. A
StatePublished - 2001
Externally publishedYes

Fingerprint

Neuronal Ceroid-Lipofuscinoses
Cysteine
Scandinavian and Nordic Countries
Lipofuscin
Protein Deficiency
Mutation
Finland
Neurodegenerative Diseases
Genes
Fatty Acids
Animal Models
Genotype
Phenotype
Ceroid lipofuscinosis, neuronal 1, infantile
Brain
Enzymes
Population
Proteins
palmitoyl-protein thioesterase

Keywords

  • Batten disease
  • Genotype-phenotype correlations
  • Lysosomal storage disorders
  • Neuronal ceroid lipofuscinosis
  • Palmitoyl-protein thioesterase

ASJC Scopus subject areas

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

Cite this

Hofmann, S. L., Das, A. K., Lu, J. Y., Wisniewski, K. E., & Gupta, P. (2001). Infantile neuronal ceroid lipofuscinosis: No longer just a 'Finnish' disease. European Journal of Paediatric Neurology, 5(SUPPL. A), 47-51.

Infantile neuronal ceroid lipofuscinosis : No longer just a 'Finnish' disease. / Hofmann, S. L.; Das, A. K.; Lu, J. Y.; Wisniewski, K. E.; Gupta, Praveena.

In: European Journal of Paediatric Neurology, Vol. 5, No. SUPPL. A, 2001, p. 47-51.

Research output: Contribution to journalArticle

Hofmann, SL, Das, AK, Lu, JY, Wisniewski, KE & Gupta, P 2001, 'Infantile neuronal ceroid lipofuscinosis: No longer just a 'Finnish' disease', European Journal of Paediatric Neurology, vol. 5, no. SUPPL. A, pp. 47-51.
Hofmann, S. L. ; Das, A. K. ; Lu, J. Y. ; Wisniewski, K. E. ; Gupta, Praveena. / Infantile neuronal ceroid lipofuscinosis : No longer just a 'Finnish' disease. In: European Journal of Paediatric Neurology. 2001 ; Vol. 5, No. SUPPL. A. pp. 47-51.
@article{55bc906e195b49338a076ef9b271e35e,
title = "Infantile neuronal ceroid lipofuscinosis: No longer just a 'Finnish' disease",
abstract = "The neuronal ceroid lipofuscinoses (NCLs) are a group of enigmatic neurodegenerative disorders of children that have in common the storage of autofluorescent lipofuscin, or aging pigment, in the brain. With the identification of the three major genes involved in the disorder, the NCLs are now appreciated to represent true lysosomal storage disorders. The most severe (infantile) form of NCL is caused by mutations in a lysosomal thioesterase that removes fatty acids from modified cysteine residues in proteins. Although the disorder was first described in Finland (and the identification of the underlying gene (CLN1) made in this population) defects in CLN1 and the underlying deficiency have been widely reported outside of Scandinavia. In this report, we summarize the relationship of genotype to phenotype in the disorder and evaluate known mutations in light of the recently solved crystal structure of defective enzyme, palmitoyl-protein thioesterase (PPT). We also discuss progress in identifying the fatty acyl cysteine thioesters that accumulate in PPT deficiency and in working toward animal models of NCL. Recent progress in these areas holds promise for the eventual treatment of the disorder.",
keywords = "Batten disease, Genotype-phenotype correlations, Lysosomal storage disorders, Neuronal ceroid lipofuscinosis, Palmitoyl-protein thioesterase",
author = "Hofmann, {S. L.} and Das, {A. K.} and Lu, {J. Y.} and Wisniewski, {K. E.} and Praveena Gupta",
year = "2001",
language = "English (US)",
volume = "5",
pages = "47--51",
journal = "European Journal of Paediatric Neurology",
issn = "1090-3798",
publisher = "W.B. Saunders Ltd",
number = "SUPPL. A",

}

TY - JOUR

T1 - Infantile neuronal ceroid lipofuscinosis

T2 - No longer just a 'Finnish' disease

AU - Hofmann, S. L.

AU - Das, A. K.

AU - Lu, J. Y.

AU - Wisniewski, K. E.

AU - Gupta, Praveena

PY - 2001

Y1 - 2001

N2 - The neuronal ceroid lipofuscinoses (NCLs) are a group of enigmatic neurodegenerative disorders of children that have in common the storage of autofluorescent lipofuscin, or aging pigment, in the brain. With the identification of the three major genes involved in the disorder, the NCLs are now appreciated to represent true lysosomal storage disorders. The most severe (infantile) form of NCL is caused by mutations in a lysosomal thioesterase that removes fatty acids from modified cysteine residues in proteins. Although the disorder was first described in Finland (and the identification of the underlying gene (CLN1) made in this population) defects in CLN1 and the underlying deficiency have been widely reported outside of Scandinavia. In this report, we summarize the relationship of genotype to phenotype in the disorder and evaluate known mutations in light of the recently solved crystal structure of defective enzyme, palmitoyl-protein thioesterase (PPT). We also discuss progress in identifying the fatty acyl cysteine thioesters that accumulate in PPT deficiency and in working toward animal models of NCL. Recent progress in these areas holds promise for the eventual treatment of the disorder.

AB - The neuronal ceroid lipofuscinoses (NCLs) are a group of enigmatic neurodegenerative disorders of children that have in common the storage of autofluorescent lipofuscin, or aging pigment, in the brain. With the identification of the three major genes involved in the disorder, the NCLs are now appreciated to represent true lysosomal storage disorders. The most severe (infantile) form of NCL is caused by mutations in a lysosomal thioesterase that removes fatty acids from modified cysteine residues in proteins. Although the disorder was first described in Finland (and the identification of the underlying gene (CLN1) made in this population) defects in CLN1 and the underlying deficiency have been widely reported outside of Scandinavia. In this report, we summarize the relationship of genotype to phenotype in the disorder and evaluate known mutations in light of the recently solved crystal structure of defective enzyme, palmitoyl-protein thioesterase (PPT). We also discuss progress in identifying the fatty acyl cysteine thioesters that accumulate in PPT deficiency and in working toward animal models of NCL. Recent progress in these areas holds promise for the eventual treatment of the disorder.

KW - Batten disease

KW - Genotype-phenotype correlations

KW - Lysosomal storage disorders

KW - Neuronal ceroid lipofuscinosis

KW - Palmitoyl-protein thioesterase

UR - http://www.scopus.com/inward/record.url?scp=0034912181&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034912181&partnerID=8YFLogxK

M3 - Article

C2 - 11589007

AN - SCOPUS:0034912181

VL - 5

SP - 47

EP - 51

JO - European Journal of Paediatric Neurology

JF - European Journal of Paediatric Neurology

SN - 1090-3798

IS - SUPPL. A

ER -