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Journal of Pediatric Biochemistry 2016; 06(01): 060-065
DOI: 10.1055/s-0036-1582222
Review Article
Georg Thieme Verlag KG Stuttgart · New York

The Neuronal Ceroid Lipofuscinoses: A Case-Based Overview

Michele Grisolia
1   Department of Medical and Surgical Sciences, Pediatric Unit, University Magna Graecia of Catanzaro, Catanzaro, Italy
,
Simona Sestito
1   Department of Medical and Surgical Sciences, Pediatric Unit, University Magna Graecia of Catanzaro, Catanzaro, Italy
,
Ferdinando Ceravolo
1   Department of Medical and Surgical Sciences, Pediatric Unit, University Magna Graecia of Catanzaro, Catanzaro, Italy
,
Federica Invernizzi
2   Unit of Molecular Neurogenetics, Institute of Neurology Foundation Carlo Besta IRCCS, Milan, Italy
,
Vincenzo Salpietro
3   Department of Pediatrics, University of Messina, Messina, Italy
4   Institute of Neurogenetics, National Hospital for Neurology and Neurosurgery, University College London Hospitals, London, United Kingdom
,
Agata Polizzi
5   National Centre for Rare Diseases, Istituto Superiore di Sanità, Rome, Italy
,
Martino Ruggieri
6   Department of Clinical and Experimental Medicine, Section of Pediatrics and Child Neuropsychiatry, University of Catania, Catania, Italy
,
Barbara Garavaglia
2   Unit of Molecular Neurogenetics, Institute of Neurology Foundation Carlo Besta IRCCS, Milan, Italy
,
Daniela Concolino
1   Department of Medical and Surgical Sciences, Pediatric Unit, University Magna Graecia of Catanzaro, Catanzaro, Italy
› Institutsangaben
Weitere Informationen

Publikationsverlauf

09. Dezember 2015

18. Januar 2016

Publikationsdatum:
26. April 2016 (online)

    Lizenzen und Reprints

Abstract

The neuronal ceroid lipofuscinoses (NCLs) are a heterogeneous group of inherited, progressive neurodegenerative diseases. Manifestations may begin between the neonatal period and young adulthood, depending on the various subtypes. The different phenotypes are similar and include visual loss, seizures, loss of motor and cognitive function, and early death. At autopsy, there is massive neuronal loss with characteristic storage in the remaining neurons. Neurons appear to die because of increased rates of apoptosis and altered autophagy as occurs in lysosomal storage diseases. A total of 13 neuronal ceroid lipofuscinoses (CLN) genetic forms have been identified so far (CLN type 1–14). In the present review, we propose a classification scheme of the major forms and report the case of a familial recurrence of NCL type 10, with a mutation in the CLN10 gene coding for the cathepsin D protein.

Keywords

neuronal ceroid lipofuscinosis - neurodegenerative diseases - CLN10
 

  • References

  • 1 Mole SE, Williams RE, Goebel HH. The Neuronal Ceroid Lipofuscinoses (Batten Disease). 2nd ed. Oxford, United Kingdom: Oxford University Press; 2011
    CrossrefSuche in Google Scholar
  • 2 Simonati A, Rizzuto N. Neuronal ceroid lipofuscinoses: pathological features of bioptic specimens from 28 patients. Neurol Sci 2000; 21 (3, Suppl): S63-S70
    CrossrefPubMedSuche in Google Scholar
  • 3 Bennett MJ, Rakheja D. The neuronal ceroid-lipofuscinoses. Dev Disabil Res Rev 2013; 17 (3) 254-259
    CrossrefPubMedSuche in Google Scholar
  • 4 Nosková L, Stránecký V, Hartmannová H , et al. Mutations in DNAJC5, encoding cysteine-string protein alpha, cause autosomal-dominant adult-onset neuronal ceroid lipofuscinosis. Am J Hum Genet 2011; 89 (2) 241-252
    CrossrefPubMedSuche in Google Scholar
  • 5 Kohlschütter A, Williams RE, Goebel HH , et al. NCL diagnosis and algorithms. In: Mole SE, Williams RE, Goebel HH, eds. The Neuronal Ceroid Lipofuscinoses (Batten Disease). 2nd ed. Oxford, United Kingdom: Oxford University Press; 2011: 24-34
    CrossrefSuche in Google Scholar
  • 6 Williams RE, Mole SE. New nomenclature and classification scheme for the neuronal ceroid lipofuscinoses. Neurology 2012; 79 (2) 183-191
    CrossrefPubMedSuche in Google Scholar
  • 7 University College London. NCL mutation and patient database. Available at: www.ucl.ac.uk/ncl/mutation.shtml . Accessed Dec 3, 2015
    PubMed
  • 8 Haltia M, Goebel HH. The neuronal ceroid-lipofuscinoses: a historical introduction. Biochim Biophys Acta 2013; 1832 (11) 1795-1800
    CrossrefPubMedSuche in Google Scholar
  • 9 Elleder M. Primary extracellular ceroid type lipopigment. A histochemical and ultrastructural study. Histochem J 1991; 23 (6) 247-258
    CrossrefPubMedSuche in Google Scholar
  • 10 Santorelli FM, Garavaglia B, Cardona F , et al. Molecular epidemiology of childhood neuronal ceroid-lipofuscinosis in Italy. Orphanet J Rare Dis 2013; 8: 19
    CrossrefPubMedSuche in Google Scholar
  • 11 Mitchison HM, Hofmann SL, Becerra CHR , et al. Mutations in the palmitoyl-protein thioesterase gene (PPT; CLN1) causing juvenile neuronal ceroid lipofuscinosis with granular osmiophilic deposits. Hum Mol Genet 1998; 7 (2) 291-297
    CrossrefPubMedSuche in Google Scholar
  • 12 Santavuori P, Vanhanen SL, Sainio K , et al. Infantile neuronal ceroid-lipofuscinosis (INCL): diagnostic criteria. J Inherit Metab Dis 1993; 16 (2) 227-229 Review
    CrossrefPubMedSuche in Google Scholar
  • 13 Steinfeld R, Heim P, von Gregory H , et al. Late infantile neuronal ceroid lipofuscinosis: quantitative description of the clinical course in patients with CLN2 mutations. Am J Med Genet 2002; 112 (4) 347-354
    CrossrefPubMedSuche in Google Scholar
  • 14 Arsov T, Smith KR, Damiano J , et al. Kufs disease, the major adult form of neuronal ceroid lipofuscinosis, caused by mutations in CLN6. Am J Hum Genet 2011; 88 (5) 566-573
    CrossrefPubMedSuche in Google Scholar
  • 15 Smith KR, Damiano J, Franceschetti S , et al. Strikingly different clinicopathological phenotypes determined by progranulin-mutation dosage. Am J Hum Genet 2012; 90 (6) 1102-1107
    CrossrefPubMedSuche in Google Scholar
  • 16 Smith KR, Dahl HH, Canafoglia L , et al. Cathepsin F mutations cause Type B Kufs disease, an adult-onset neuronal ceroid lipofuscinosis. Hum Mol Genet 2013; 22 (7) 1417-1423
    CrossrefPubMedSuche in Google Scholar
  • 17 Schulz A, Dhar S, Rylova S , et al. Impaired cell adhesion and apoptosis in a novel CLN9 Batten disease variant. Ann Neurol 2004; 56 (3) 342-350
    CrossrefPubMedSuche in Google Scholar
  • 18 Siintola E, Partanen S, Strömme P , et al. Cathepsin D deficiency underlies congenital human neuronal ceroid-lipofuscinosis. Brain 2006; 129 (Pt 6) 1438-1445
    CrossrefPubMedSuche in Google Scholar
  • 19 Hersheson J, Burke D, Clayton R , et al. Cathepsin D deficiency causes juvenile-onset ataxia and distinctive muscle pathology. Neurology 2014; 83 (20) 1873-1875
    CrossrefPubMedSuche in Google Scholar
  • 20 Bras J, Verloes A, Schneider SA, Mole SE, Guerreiro RJ. Mutation of the parkinsonism gene ATP13A2 causes neuronal ceroid-lipofuscinosis. Hum Mol Genet 2012; 21 (12) 2646-2650
    CrossrefPubMedSuche in Google Scholar
  • 21 Ramirez A, Heimbach A, Gründemann J , et al. Hereditary parkinsonism with dementia is caused by mutations in ATP13A2, encoding a lysosomal type 5 P-type ATPase. Nat Genet 2006; 38 (10) 1184-1191
    CrossrefPubMedSuche in Google Scholar
  • 22 Staropoli JF, Karaa A, Lim ET , et al. A homozygous mutation in KCTD7 links neuronal ceroid lipofuscinosis to the ubiquitin-proteasome system. Am J Hum Genet 2012; 91 (1) 202-208
    CrossrefPubMedSuche in Google Scholar
  • 23 Mole SE, Williams RE, Neuronal ceroid-lipofuscinoses. In: Pagon RA, Adam MP, Ardinger HH. , et al., eds. Seattle (WA): University of Washington, Seattle; 1993. –2015
    Suche in Google Scholar
  • 24 Tomanin R, Zanetti A, D'Avanzo F , et al. Clinical efficacy of enzyme replacement therapy in paediatric Hunter patients, an independent study of 3.5 years. Orphanet J Rare Dis 2014; 9: 129
    CrossrefPubMedSuche in Google Scholar
  • 25 Parini R, Rigoldi M, Santus F , et al. Enzyme replacement therapy with agalsidase alfa in a cohort of Italian patients with Anderson-Fabry disease: testing the effects with the Mainz Severity Score Index. Clin Genet 2008; 74 (3) 260-266
    CrossrefPubMedSuche in Google Scholar
  • 26 Sechi A, Deroma L, Dardis A , et al. Long term effects of enzyme replacement therapy in an Italian cohort of type 3 Gaucher patients. Mol Genet Metab 2014; 113 (3) 213-218
    CrossrefPubMedSuche in Google Scholar
  • 27 Lu JY, Nelvagal HR, Wang L, Birnbaum SG, Cooper JD, Hofmann SL. Intrathecal enzyme replacement therapy improves motor function and survival in a preclinical mouse model of infantile neuronal ceroid lipofuscinosis. Mol Genet Metab 2015; 116 (1–2) 98-105
    CrossrefPubMedSuche in Google Scholar
  • 28 Neverman NJ, Best HL, Hofmann SL, Hughes SM. Experimental therapies in the neuronal ceroid lipofuscinoses. Biochim Biophys Acta 2015; 1852 (10 Pt B): 2292-2300
    CrossrefPubMedSuche in Google Scholar