Disease report

Tree Display

AceDB Schema

XML Display


Disease Report for: Infantile neuronal ceroid lipofuscinosis

Alternative name(s)|Ceroid lipofuscinosis, juvenile neuronal, with granular osmiophilic deposits
CLN1 gene product deficiency
Palmitoyl-protein thioesterase 1 deficiency
PPT1 deficiency
Neuronal ceroid lipofuscinosis, infantile finnish type; NCL
Santavuori disease
Santavuori-Haltia disease
Ceroid lipofuscinosis, neuronal 1, adult
Mutation|73 mutations (e.g. : C152X_human-PPT1, C152Y_human-PPT1, C45Y_human-PPT1... more)
OMIM: |600722, 256730

Goebel (1995) provided a comprehensive review of the neuronal ceroid lipofuscinoses, possibly the most common group of neurodegenerative diseases in children. They are characterized by intralysosomal accumulations of lipopigments in either granular, curvilinear, or fingerprint patterns. These include infantile Santavuori-Haltia disease, late infantile Jansky-Bielschowsky disease (204500), late infantile form (256731), juvenile Vogt-Spielmeyer disease (or Batten disease; 204200), and Kufs disease (204300), as well as approximately a dozen atypical variants. The clinical course is that of progressive dementia, seizures, and progressive visual failure. Using 'Batten disease' as a generic collective designation for the neuronal ceroid lipofuscinoses, Mole (1999) stated that 8 genes causing the different varieties had been identified. She posed the question of whether other genes causing these diseases remained to be identified. The genes CLN1 (PPT1) and CLN2 (204500), which are mutant in the infantile and late-infantile forms of neuronal ceroid lipofuscinosis, respectively, encode lysosomal enzymes; the CLN3 (607042) and CLN5 (256731) genes, which are mutant in the juvenile form (Batten disease; 204200) and Finnish-variant neuronal ceroid lipofuscinosis (256731), respectively, encode membrane-spanning proteins. Zhong et al. (2000) addressed the question of why deficiencies of lysosomal enzymes and membrane-spanning proteins produce similar clinical phenotypes and pathologic changes. They hypothesized that CLN-encoded proteins may comprise a functional pathogenic pathway in which protein associations play important roles. To test this hypothesis, they studied protein-protein interactions among the CLN1-, CLN2-, and CLN3-encoded proteins using a yeast 2-hybrid system. Results provided no evidence that CLN-encoded proteins interact with each other. NCL Mutation and Patient Database NCL

    Title: Computational and structural investigation of Palmitoyl-Protein Thioesterase 1 (PPT1) protein causing Neuronal Ceroid Lipofuscinoses (NCL)
    Thirumal Kumar D, Shaikh N, Udhaya Kumar S, George Priya Doss C
    Ref: Advances in Protein Chemistry Struct Biol, 132:89, 2022 : PubMed


    Title: Detection of Infantile Batten Disease by Tandem Mass Spectrometry Assay of PPT1 Enzyme Activity in Dried Blood Spots
    Khaledi H, Liu Y, Masi S, Gelb MH
    Ref: Analytical Chemistry, 90:12168, 2018 : PubMed


    Title: Moving towards effective therapeutic strategies for Neuronal Ceroid Lipofuscinosis
    Geraets RD, Koh S, Hastings ML, Kielian T, Pearce DA, Weimer JM
    Ref: Orphanet J Rare Dis, 11:40, 2016 : PubMed


    Metelitsina TI, Waggoner DJ, Grassi MA
    Ref: Retin Cases Brief Rep, 10:211, 2016 : PubMed


    Title: A girl with infantile neuronal ceroid lipofuscinosis caused by novel PPT1 mutation and paternal uniparental isodisomy of chromosome 1
    Niida Y, Yokoi A, Kuroda M, Mitani Y, Nakagawa H, Ozaki M
    Ref: Brain Dev, 38:674, 2016 : PubMed


    Title: Analysis of large-scale whole exome sequencing data to determine the prevalence of genetically-distinct forms of neuronal ceroid lipofuscinosis
    Sleat DE, Gedvilaite E, Zhang Y, Lobel P, Xing J
    Ref: Gene, 593:284, 2016 : PubMed


    Title: The neuronal ceroid lipofuscinoses program: A translational research experience in Argentina
    Kohan R, Pesaola F, Guelbert N, Pons P, Oller-Ramirez AM, Rautenberg G, Becerra A, Sims K, Xin W and Noher de Halac I <1 more author(s)>
    Ref: Biochimica & Biophysica Acta, 1852:2301, 2015 : PubMed


    Title: Human pathology in NCL
    Anderson GW, Goebel HH, Simonati A
    Ref: Biochimica & Biophysica Acta, 1832:1807, 2013 : PubMed


    Title: Neuronal ceroid lipofuscinosis: impact of recent genetic advances and expansion of the clinicopathologic spectrum
    Cotman SL, Karaa A, Staropoli JF, Sims KB
    Ref: Curr Neurol Neurosci Rep, 13:366, 2013 : PubMed


    Title: Pathogenesis and therapies for infantile neuronal ceroid lipofuscinosis (infantile CLN1 disease)
    Hawkins-Salsbury JA, Cooper JD, Sands MS
    Ref: Biochimica & Biophysica Acta, 1832:1906, 2013 : PubMed


    Title: A novel c.776_777insA mutation in CLN1 leads to infantile neuronal ceroid lipofuscinosis
    Miller JN, Pearce DA
    Ref: Journal of Child Neurology, 28:1106, 2013 : PubMed


    Title: Molecular epidemiology of childhood neuronal ceroid-lipofuscinosis in Italy
    Santorelli FM, Garavaglia B, Cardona F, Nardocci N, Bernardina BD, Sartori S, Suppiej A, Bertini E, Claps D and Simonati A <4 more author(s)>
    Ref: Orphanet J Rare Dis, 8:19, 2013 : PubMed


    Title: NCL diseases - clinical perspectives
    Schulz A, Kohlschutter A, Mink J, Simonati A, Williams R
    Ref: Biochimica & Biophysica Acta, 1832:1801, 2013 : PubMed


    Title: Atypical juvenile neuronal ceroid lipofuscinosis: A report of three cases
    Setty G, Saleem R, Khan A, Hussain N
    Ref: J Pediatr Neurosci, 8:117, 2013 : PubMed


    Title: Genetic basis and phenotypic correlations of the neuronal ceroid lipofusinoses
    Warrier V, Vieira M, Mole SE
    Ref: Biochimica & Biophysica Acta, 1832:1827, 2013 : PubMed


    Title: Update of the mutation spectrum and clinical correlations of over 360 mutations in eight genes that underlie the neuronal ceroid lipofuscinoses
    Kousi M, Lehesjoki AE, Mole SE
    Ref: Hum Mutat, 33:42, 2012 : PubMed


    Title: Infantile neuronal ceroid lipofuscinosis: follow-up on a Spanish series
    Perez Poyato MS, Mila Recansens M, Ferrer Abizanda I, Domingo Jimenez R, Lopez Lafuente A, Cusi Sanchez V, Rodriguez-Revenga L, Coll Rosell MJ, Gort L and Pineda Marfa M <1 more author(s)>
    Ref: Gene, 499:297, 2012 : PubMed


    Title: Therapeutic approaches to the challenge of neuronal ceroid lipofuscinoses
    Kohan R, Cismondi IA, Oller-Ramirez AM, Guelbert N, Anzolini TV, Alonso G, Mole SE, de Kremer DR, de Halac NI
    Ref: Curr Pharm Biotechnol, 12:867, 2011 : PubMed


    Title: Palmitoyl:protein thioesterase (PPT1) inhibitors can act as pharmacological chaperones in infantile Batten disease
    Dawson G, Schroeder C, Dawson PE
    Ref: Biochemical & Biophysical Research Communications, 395:66, 2010 : PubMed


    Title: Novel human pathological mutations. Gene symbol: PPT1. Disease: neuronal ceroid lipofuscinosis, juvenile
    Mueller OT, Coovadia A
    Ref: Hum Genet, 127:490, 2010 : PubMed


    Title: An integrated strategy for the diagnosis of neuronal ceroid lipofuscinosis types 1 (CLN1) and 2 (CLN2) in eleven Latin American patients
    Kohan R, Cismondi IA, Kremer RD, Muller VJ, Guelbert N, Anzolini VT, Fietz MJ, Ramirez AM, Halac IN
    Ref: Clin Genet, 76:372, 2009 : PubMed


    Title: Variant late infantile neuronal ceroid lipofuscinosis because of CLN1 mutations
    Simonati A, Tessa A, Bernardina BD, Biancheri R, Veneselli E, Tozzi G, Bonsignore M, Grosso S, Piemonte F, Santorelli FM
    Ref: Pediatr Neurol, 40:271, 2009 : PubMed


    Title: Juvenile-onset neuronal ceroid lipofuscinosis with infantile CLN1 mutation and palmitoyl-protein thioesterase deficiency
    Kalviainen R, Eriksson K, Losekoot M, Sorri I, Harvima I, Santavuori P, Jarvela I, Autti T, Vanninen R and van Diggelen OP <1 more author(s)>
    Ref: Eur Journal of Neurology, 14:369, 2007 : PubMed


    Title: Adult neuronal ceroid lipofuscinosis caused by deficiency in palmitoyl protein thioesterase 1
    Ramadan H, Al-Din AS, Ismail A, Balen F, Varma A, Twomey A, Watts R, Jackson M, Anderson G and Mole SE <1 more author(s)>
    Ref: Neurology, 68:387, 2007 : PubMed


    Title: [Two novel mutations in palmitoyl-protein thioesterase gene in two Chinese babies with infantile neuronal ceroid lipofuscinosis]
    Bi HY, Yao S, Bu DF, Wang ZX, Zhang Y, Qin J, Yang YL, Yuan Y
    Ref: Zhonghua Er Ke Za Zhi, 44:496, 2006 : PubMed


    Title: Novel CLN1 mutation in two Italian sibs with late infantile neuronal ceroid lipofuscinosis
    Bonsignore M, Tessa A, Di Rosa G, Piemonte F, Dionisi-Vici C, Simonati A, Calamoneri F, Tortorella G, Santorelli FM
    Ref: Eur J Paediatr Neurol, 10:154, 2006 : PubMed


    Title: Palmitoyl Protein Thioesterase1 (PPT1) and Tripeptidyl Peptidase-I (TPP-I) are expressed in the human saliva. A reliable and non-invasive source for the diagnosis of infantile (CLN1) and late infantile (CLN2) neuronal ceroid lipofuscinoses
    Kohan R, Noher de Halac I, Tapia Anzolini V, Cismondi A, Oller Ramirez AM, Paschini Capra A, de Kremer RD
    Ref: Clinical Biochemistry, 38:492, 2005 : PubMed


    Title: [From gene to disease; from CLN1, CLN2 and CLN3 to neuronal ceroid lipofuscinosis]
    Taschner PE, Losekoot M, Breuning MH, Hofman I, van Diggelen OP
    Ref: Ned Tijdschr Geneeskd, 149:300, 2005 : PubMed


    Title: High-resolution magic angle spinning and 1H magnetic resonance spectroscopy reveal significantly altered neuronal metabolite profiles in CLN1 but not in CLN3
    Sitter B, Autti T, Tyynela J, Sonnewald U, Bathen TF, Puranen J, Santavuori P, Haltia MJ, Paetau A and Hakkinen AM <2 more author(s)>
    Ref: Journal of Neuroscience Research, 77:762, 2004 : PubMed


    Title: Clinicopathological and molecular characterization of neuronal ceroid lipofuscinosis in the Portuguese population
    Teixeira C, Guimaraes A, Bessa C, Ferreira MJ, Lopes L, Pinto E, Pinto R, Boustany RM, Sa Miranda MC, Ribeiro MG
    Ref: Journal of Neurology, 250:661, 2003 : PubMed


    Title: A novel mutation in the CLN1 gene in a patient with juvenile neuronal ceroid lipofuscinosis
    Mazzei R, Conforti FL, Magariello A, Bravaccio C, Militerni R, Gabriele AL, Sampaolo S, Patitucci A, Di Iorio G and Quattrone A <1 more author(s)>
    Ref: Journal of Neurology, 249:1398, 2002 : PubMed


    Title: Biochemical analysis of mutations in palmitoyl-protein thioesterase causing infantile and late-onset forms of neuronal ceroid lipofuscinosis
    Das AK, Lu JY, Hofmann SL
    Ref: Hum Mol Genet, 10:1431, 2001 : PubMed


    Title: Disruption of PPT1 or PPT2 causes neuronal ceroid lipofuscinosis in knockout mice
    Gupta P, Soyombo AA, Atashband A, Wisniewski KE, Shelton JM, Richardson JA, Hammer RE, Hofmann SL
    Ref: Proc Natl Acad Sci U S A, 98:13566, 2001 : PubMed


    Title: Palmitoyl protein thioesterase (PPT) localizes into synaptosomes and synaptic vesicles in neurons: implications for infantile neuronal ceroid lipofuscinosis (INCL)
    Lehtovirta M, Kyttala A, Eskelinen EL, Hess M, Heinonen O, Jalanko A
    Ref: Hum Mol Genet, 10:69, 2001 : PubMed


    Title: New mutations in the neuronal ceroid lipofuscinosis genes
    Mole SE, Zhong NA, Sarpong A, Logan WP, Hofmann S, Yi W, Franken PF, van Diggelen OP, Breuning MH and Taschner PE <5 more author(s)>
    Ref: Eur J Paediatr Neurol, 5 Suppl A:7, 2001 : PubMed


    Title: Adult neuronal ceroid lipofuscinosis with palmitoyl-protein thioesterase deficiency: first adult-onset patients of a childhood disease
    van Diggelen OP, Thobois S, Tilikete C, Zabot MT, Keulemans JL, van Bunderen PA, Taschner PE, Losekoot M, Voznyi YV
    Ref: Annals of Neurology, 50:269, 2001 : PubMed


    Title: The crystal structure of palmitoyl protein thioesterase 1 and the molecular basis of infantile neuronal ceroid lipofuscinosis
    Bellizzi JJ, 3rd, Widom J, Kemp C, Lu JY, Das AK, Hofmann SL, Clardy J
    Ref: Proc Natl Acad Sci U S A, 97:4573, 2000 : PubMed


    Title: Expression of palmitoyl protein thioesterase in neurons.
    Heinonen O, Kyttala A, Lehmus E, Paunio T, Peltonen L, Jalanko A
    Ref: Molec Genet Metab, 69:123, 2000 : PubMed


    Title: Detection of eight novel palmitoyl protein thioesterase (PPT) mutations underlying infantile neuronal ceroid lipofuscinosis (INCL;CLN1)
    Salonen T, Jarvela I, Peltonen L, Jalanko A
    Ref: Hum Mutat, 15:273, 2000 : PubMed


    Title: Identification of three novel mutations of the palmitoyl-protein thioesterase-1 (PPT1) gene in children with neuronal ceroid-lipofuscinosis
    Waliany S, Das AK, Gaben A, Wisniewski KE, Hofmann SL
    Ref: Hum Mutat, 15:206, 2000 : PubMed


    Title: CLN-encoded proteins do not interact with each other
    Zhong NA, Moroziewicz DN, Ju W, Wisniewski KE, Jurkiewicz A, Brown WT
    Ref: Neurogenetics, 3:41, 2000 : PubMed


    Title: Molecular basis of the neuronal ceroid lipofuscinoses: mutations in CLN1, CLN2, CLN3, and CLN5
    Mole SE, Mitchison HM, Munroe PB
    Ref: Hum Mutat, 14:199, 1999 : PubMed


    Title: Batten's disease: eight genes and still counting?
    Mole SE
    Ref: Lancet, 354:443, 1999 : PubMed


    Title: Genetic heterogeneity of neuronal ceroid lipofuscinosis in The Netherlands
    Taschner PE, Franken PF, van Berkel L, Breuning MH
    Ref: Mol Genet Metab, 66:339, 1999 : PubMed


    Title: A new simple enzyme assay for pre- and postnatal diagnosis of infantile neuronal ceroid lipofuscinosis (INCL) and its variants
    Voznyi YV, Keulemans JL, Mancini GM, Catsman-Berrevoets CE, Young E, Winchester B, Kleijer WJ, van Diggelen OP
    Ref: Journal of Medical Genetics, 36:471, 1999 : PubMed


    Title: First-trimester diagnosis of infantile neuronal ceroid lipofuscinosis (INCL) using PPT enzyme assay and CLN1 mutation analysis
    de Vries BB, Kleijer WJ, Keulemans JL, Voznyi YV, Franken PF, Eurlings MC, Galjaard RJ, Losekoot M, Catsman-Berrevoets CE and van Diggelen OP <2 more author(s)>
    Ref: Prenat Diagn, 19:559, 1999 : PubMed


    Title: Molecular genetics of palmitoyl-protein thioesterase deficiency in the U.S
    Das AK, Becerra CH, Yi W, Lu JY, Siakotos AN, Wisniewski KE, Hofmann SL
    Ref: Journal of Clinical Investigation, 102:361, 1998 : PubMed


    Title: Mutations in the palmitoyl-protein thioesterase gene (PPT; CLN1) causing juvenile neuronal ceroid lipofuscinosis with granular osmiophilic deposits
    Mitchison HM, Hofmann SL, Becerra CH, Munroe PB, Lake BD, Crow YJ, Stephenson JB, Williams RE, Hofman IL and O'Rawe AM <7 more author(s)>
    Ref: Hum Mol Genet, 7:291, 1998 : PubMed


    Title: Sharing of PPT mutations between distinct clinical forms of neuronal ceroid lipofuscinoses in patients from Scotland
    Munroe PB, Greene ND, Leung KY, Mole SE, Gardiner RM, Mitchison HM, Stephenson JB, Crow YJ
    Ref: Journal of Medical Genetics, 35:790, 1998 : PubMed


    Title: A novel insertion mutation (A169i) in the CLN1 gene is associated with infantile neuronal ceroid lipofuscinosis in an Italian patient
    Santorelli FM, Bertini E, Petruzzella V, Di Capua M, Calvieri S, Gasparini P, Zeviani M
    Ref: Biochemical & Biophysical Research Communications, 245:519, 1998 : PubMed


    Title: cDNA and genomic cloning of human palmitoyl-protein thioesterase (PPT), the enzyme defective in infantile neuronal ceroid lipofuscinosis
    Schriner JE, Yi W, Hofmann SL
    Ref: Genomics, 34:317, 1996 : PubMed


    Title: The neuronal ceroid-lipofuscinoses
    Goebel HH
    Ref: Journal of Child Neurology, 10:424, 1995 : PubMed


    Title: Identification of YAC clones for human chromosome 1p32 and physical mapping of the infantile neuronal ceroid lipofuscinosis (INCL) locus
    Hellsten E, Vesa J, Heiskanen M, Makela TP, Jarvela I, Cowell JK, Mead S, Alitalo K, Palotie A, Peltonen L
    Ref: Genomics, 25:404, 1995 : PubMed


    Title: MRI evaluation of the brain in infantile neuronal ceroid-lipofuscinosis. Part 2: MRI findings in 21 patients
    Vanhanen SL, Raininko R, Autti T, Santavuori P
    Ref: Journal of Child Neurology, 10:444, 1995 : PubMed


    Title: Mutations in the palmitoyl protein thioesterase gene causing infantile neuronal ceroid lipofuscinosis
    Vesa J, Hellsten E, Verkruyse LA, Camp LA, Rapola J, Santavuori P, Hofmann SL, Peltonen L
    Ref: Nature, 376:584, 1995 : PubMed


    Title: Molecular cloning and expression of palmitoyl-protein thioesterase
    Camp LA, Verkruyse LA, Afendis SJ, Slaughter CA, Hofmann SL
    Ref: Journal of Biological Chemistry, 269:23212, 1994 : PubMed


    Title: Refined assignment of the infantile neuronal ceroid lipofuscinosis (INCL, CLN1) locus at 1p32: incorporation of linkage disequilibrium in multipoint analysis
    Hellsten E, Vesa J, Speer MC, Makela TP, Jarvela I, Alitalo K, Ott J, Peltonen L
    Ref: Genomics, 16:720, 1993 : PubMed


    Title: Infantile neuronal ceroid lipofuscinosis (CLN1): linkage disequilibrium in the Finnish population and evidence that variant late infantile form (variant CLN2) represents a nonallelic locus
    Jarvela I
    Ref: Genomics, 10:333, 1991 : PubMed


    Title: Assignment of the infantile form of neuronal ceroid lipofuscinosis (INCL, CLN1) to the short arm of chromosome 1 (Abstract)
    Jarvela I, Santavuori P, Vesa J, Rapola J, Palotie A, Peltonen L
    Ref: Cytogenet Cell Genet, 58:1856, 1991 : PubMed


    Title: Infantile form of neuronal ceroid lipofuscinosis (CLN1) maps to the short arm of chromosome 1
    Jarvela I, Schleutker J, Haataja L, Santavuori P, Puhakka L, Manninen T, Palotie A, Sandkuijl LA, Renlund M and et al. <1 more author(s)>
    Ref: Genomics, 9:170, 1991 : PubMed


    Title: Infantile neuronal ceroid-lipofuscinosis is not an allelic form of Batten disease: exclusion of chromosome 16 region with linkage analyses
    Jokiaho I, Puhakka L, Santavuori P, Manninen T, Nyman K, Peltonen L
    Ref: Genomics, 8:391, 1990 : PubMed


    Title: Santavuori disease: diagnosis by leukocyte ultrastructure
    Baumann RJ, Markesbery WR
    Ref: Neurology, 32:1277, 1982 : PubMed


    Title: Clinical, morphological, and biochemical investigations on a patient with an unusual form of neuronal ceroid-lipofuscinosis
    Becker K, Goebel HH, Svennerholm L, Wendel U, Bremer HJ
    Ref: Eur J Pediatr, 132:197, 1979 : PubMed


    Title: Polyunsaturated fatty acid lipidosis infantile form of so-called neuronal ceroidlipofuscinosis
    Hagberg B, Haltia M, Sourander P, Svennerholm L, Eeg-Olofsson O
    Ref: Acta Paediatr Scand, 63:753, 1974 : PubMed


    Title: Infantile type of so-called neuronal ceroid-lipofuscinosis
    Santavuori P, Haltia M, Rapola J
    Ref: Dev Med Child Neurol, 16:644, 1974 : PubMed


    Title: Infantile type of so-called neuronal ceroid-lipofuscinosis. 2. Morphological and biochemical studies
    Haltia M, Rapola J, Santavuori P, Keranen A
    Ref: Journal of Neurology Sci, 18:269, 1973 : PubMed


    Title: Infantile type of so-called neuronal ceroid-lipofuscinosis. 1. A clinical study of 15 patients
    Santavuori P, Haltia M, Rapola J, Raitta C
    Ref: Journal of Neurology Sci, 18:257, 1973 : PubMed


    Title: Neuronal ceroid-lipofuscinosis (Batten's disease): relationship to amaurotic family idiocy?
    Zeman W, Dyken P
    Ref: Pediatrics, 44:570, 1969 : PubMed


    Title: Late infantile progressive encephalopathy with disturbed poly-unsaturated fat metabolism
    Hagberg B, Sourander P, Svennerholm L
    Ref: Acta Paediatr Scand, 57:495, 1968 : PubMed


Send your questions or comments to :
Mail to: Nicolas Lenfant, Thierry Hotelier, Yves Bourne, Pascale Marchot and Arnaud Chatonnet.
Please cite: Lenfant 2013 Nucleic.Acids.Res. or Marchot Chatonnet 2012 Prot.Pept Lett.
For technical information about these pages see:
ESTHER Home Page and ACEDB Home Page
AcePerl Lincoln Stein Home Page

Acknowledgements and disclaimer