Neuronal ceroid lipofuscinoses caused by defects in soluble lysosomal enzymes (CLN1 and CLN2).
Infantile and classical late infantile neuronal ceroid lipofuscinoses (NCL) are two recent additions to the expanding spectrum of lysosomal storage disorders caused by deficiencies in lysosomal hydrolases. They are latecomers to the lysosomal storage disorders, probably because of the heterogeneous nature of the storage material, which precluded meaningful biochemical analysis. Infantile NCL is caused by deficiency in palmitoyl-protein thioesterase, an enzyme that hydrolyzes fatty acids from cysteine residues in lipid-modified proteins. Classical late-infantile NCL is caused by a deficiency in tripeptidyl amino peptidase-I, a lysosomal peptidase that removes three amino acids from the free amino terminus of peptides or small proteins. Late-onset forms of these disorders have been described. The clinical, biochemical, and molecular genetic aspects of these two latest lysosomal storage disorders are discussed in this review. In addition, approaches to treatment and future directions for research are examined.
Hofmann
Sandra L
SL
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75390-8593, USA. Sandra.Hofmann@UTSouthwestern.edu
Atashband
Armita
A
Cho
Steve K
SK
Das
Amit K
AK
Gupta
Praveena
P
Lu
Jui-Yun
JY
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000626:Aminopeptidases; D002648:Child; D002675:Child, Preschool; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D010450:Endopeptidases; D006801:Humans; D007223:Infant; D007962:Leukocytes / Q000648:ultrastructure; D008565:Membrane Proteins / Q000235:genetics*; D008854:Microscopy, Electron; D009154:Mutation; D009472:Neuronal Ceroid-Lipofuscinoses / Q000201:enzymology / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D010447:Peptide Hydrolases / Q000235:genetics*; D011110:Polymorphism, Genetic; D057057:Serine Proteases; D013869:Thiolester Hydrolases; D000091346:Tripeptidyl-Peptidase 1
D008565:Membrane Proteins; D000091346:Tripeptidyl-Peptidase 1; D013869:Thiolester Hydrolases; C416054:PPT1 protein, human; D010450:Endopeptidases; D010447:Peptide Hydrolases; D057057:Serine Proteases; D000626:Aminopeptidases; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; C000717267:TPP1 protein, human