eMedicine Specialties > Neurology > Pediatric Neurology

Neuronal Ceroid Lipofuscinoses

Author: Celia H Chang, MD, Associate Health Sciences Clinical Professor, Department of Neurology, University of California at Davis
Contributor Information and Disclosures

Updated: Sep 17, 2009

Introduction

Background

The neuronal ceroid lipofuscinoses (NCLs), also known as Batten disease, are a group of neurodegenerative disorders. They are considered the most common of the neurogenetic storage diseases with a prevalence of 1 in 12,500 in some populations. They are associated with variable yet progressive symptoms including seizures, dementia, visual loss, and/or cerebral atrophy. In 1826, Stengel described the first patients—4 siblings in Norway. Batten made the first clinicopathologic correlation in 1903 and referred to NCL as familial cerebromacular degeneration. Batten was also the first person to differentiate NCL from Tay-Sachs disease in 1914. Vogt, Spielmeyer, Bielschowsky, and Kufs also described older patients with similar symptoms.

In 1939, Klenk discovered increased gangliosides in Tay-Sachs disease but in not juvenile amaurotic idiocy (an early name for NCL). NCL was later so named because of the accumulation of autofluorescent lipopigments resembling ceroid and lipofuscin. In 1959, Koppang described English setters with the same phenotype as patients with NCL. Although NCLs are generally autosomal recessive disorders, in 1971 Boehme also described autosomal dominant inheritance of the same disease in the Parry family of New Jersey. The enzymatic abnormalities were better defined in the 1980s and the molecular genetics have now being described in some variants of NCL. A database of NCL mutations is maintained and can be found here.1

Pathophysiology

The NCLs are almost all characterized by apoptosis and dysregulated sphingolipid metabolism. It is suspected that there are common pathways for many of the variants. Persaud-Sawin et al found that transfecting CLN1 or CLN2 deficient cells with CLN DNA constructs for either CLN1 or CLN2 was somewhat protective against etoposide-induced apoptosis in both cells types. CLN6 and CLN8 constructions resulted in near total correction of growth defects in CLN3 deficient cells and CLN2 DNA constructs were partially effective. CLN2, CLN3, and CLN8 constructs corrected growth for CLN6 deficient cells. CLN2, CLN3, and CLN6 constructs also corrected growth for CLN8 deficient cells.2

In CLN1, a lysosomal enzyme, palmitoyl protein thioesterase 1 (PPT1) is deficient. PPT1, which removes fatty acyl groups from cysteine residues on fatty acid modified proteins, remains in the endoplasmic reticulum where it is inactive, causing sapsosins A and D to accumulate in the lysosomes. Mutations have been found in all 9 exons of the CLN1 gene. Although CLN1 usually had onset in infancy, later onset (including in adulthood) has also been described. More than 49 mutations have been described in CLN1.1 Lyly et al found that glycosylation of N197 and N232, but not N212 is essential for PPT1s activity and intracellular transport. They also found that PPT1 formed oligomers. They believe that mutations cause more glycosylation and complex formation.3

Subunit C of the mitochondrial ATP synthase complex accumulates in the lysosomes of patients with some variants of NCL, including CLN2, CLN3, CLN4, CLN5, CLN6, CLN7, and CLN8. Subunit C also accumulates in some animal models of NCL, including the bovine and several canine variants. Subunit C, an extremely hydrophobic 75-amino-acid protein, is encoded by 2 separate genes, P1 and P2. P1 is on chromosome 17 and P2 is on chromosome 12. The mRNA for P2 is the predominant form. Subunit C is part of a transmembrane proton channel located on the inner mitochondrial membrane. Each ATP synthase complex has 10-12 copies of subunit C.

Patients with CLN2 are deficient in a pepstatin-insensitive lysosomal peptidase—tripeptidyl peptidase 1 (TTP1). TTP1 removes tripeptides from the N -terminal of polypeptides. Mutations have been reported in all 13 exons of the CLN2 gene. Some mutations result in a more protracted course. Although onset is usually in late infancy, later onset has been described. More than 58 mutations have been described in CLN2.1

The CLN3 gene encodes a 438 amino acid protein that is thought to be a part of the lysosomal membrane. The most common mutation of CLN3 is a 1.02-kb deletion that involves loss of exons 7 and 8. Most patients with the classic phenotype of JNCL are homozygous for the 1.02-kb deletion. Patients who are compound heterozygotes for this deletion may have atypical phenotypes. Munroe reported 2 patients who were compound heterozygotes with visual failure, only one of whom had seizures; both patients were able to hold full-time employment as adults. Wisniewski et al reported similar patients who initially presented with psychiatric or behavioral symptoms but otherwise had a typical course. More than 42 mutations1 have been described in CLN3. The exact function of CLN3 is unknown, but its expression is highest in secretory/glandular tissues and in gastrointestinal cells. All patients with CLN3 have had visual failure by age 10.

The adult form of NCL (ANCL) is associated with mutations of the CLN4 gene. The CLN4 gene has not been mapped yet.

Mutations in another gene, CLN5 is associated with Finnish variant LINCL (fLINCL). It occurs predominantly in the Finnish population. CLN5 encodes a 407 amino acid transmembrane protein. CLN5 only occurs in vertebrae. The expression of CLN5 increases during cortical neurogenesis. More than 17 mutations have been described in CLN5.1

The CLN6 gene is associated with variant LINCL (vLINCL). Disease caused by CLN6 mutations are also referred to as the Czech or Indian variant. The CLN6 gene has been mapped to band 15q21-q23 and encodes a 311 amino acid membrane protein. More than 36 mutations have been described in CLN6.1 Affected individuals with CLN6 mutations are primarily of Portuguese, Indian, Pakistani, or Czech ancestry.

The CLN7 gene has been assigned to the tLINCL variant. Individuals with the tLINCL variant were thought to originate from Turkey. Siintola et al identified 6 mutations in 5 families, 4 Turkish families and 1 Indian family, in the MFSD8 gene. The authors mapped the locus to 4q28.1-q28.2. The gene encodes a 518 amino acid membrane protein that belongs to the major facilitator superfamily of transporter proteins. MFSD8 localizes mainly to the lysosomal compartment and is ubiquitously expressed.4 Eight disease-causing mutations have been identified.1

CLN8 encodes a 286 amino acid transmembrane protein, which localizes to the endoplasmic reticulum and endoplasmic reticulum-Golgi intermediate complex. The exact function of the CLN8 protein is unknown. More than 11 mutations have been described in CLN8.1 Some mutations cause vLINCL, but missense mutations (c.70C>G for p.Arg24Gly and c.709G>A for p.Gly237Arg in association with c.70C>G) can also result in progressive epilepsy with mental retardation (PEMR) or Northern epilepsy, which is a protracted disease.

Schulz et al reported that CLN9 produces a protein that may be a regulator of dihydroceramide synthetase. Even though the CLN8 sequence was normal, transfection with CLN8 corrected growth and apoptosis in CLN9 deficient cells.

Two putative disease-causing mutations have also been identified for CLCN6.1

Frequency

United States

Estimates suggest that approximately 25,000 families in the United States are affected with a form of NCL.

International

CLN1: In the Finnish population, incidence is 1 in 20,000 with a carrier frequency of 1 in 70.

CLN2: Worldwide prevalence is 0.6-0.7 per million inhabitants, with an incidence of 0.46 per 100,000 live births.

CLN3: Worldwide, CLN3 is the second most common form of NCL. Incidence is 7 cases per 100,000 live births in Iceland.

Mortality/Morbidity

Patients with NCL have shortened life expectancy; impact on life span clearly depends on the type of NCL.

Race

The prevalence of NCL is highest in the Scandinavian countries, especially Finland, where the estimated carrier frequency is a little less than 1 in 100 or 1%.

Age

Although the age of onset depends in part upon the type of NCL, molecular genetic discoveries have revealed more clinical overlap than was appreciated previously.

Most cases of CLN1 in the Finnish population have an infantile onset. Only 50% of the CLN1 cases have an infantile onset in the United States. The other cases have late infantile, juvenile, or adult onset.

Clinical

History

The NCLs originally were defined by their age of onset and clinical symptoms; however, they have now been reclassified on the basis of newer molecular findings, which have provided evidence of far more overlap for the different genetic variants than what was previously suggested by the clinical phenotypes.

  • CLN1 or Santavuori-Haltia type or infantile NCL
    • Infantile phenotype
      • Retarded head growth
      • Hypotonia
      • Hyperexcitability
      • Cognitive dysfunction
      • Visual failure
      • Ataxia
      • Extrapyramidal movements
      • Spasticity
      • Myoclonus
      • Loss of light perception at age 2 years
      • Loss of motor and social skills at age 3 years
      • Death between age 6-13 years
    • Late infantile phenotype
      • Cognitive decline, epilepsy, visual loss at age 1.5-3.5 years
      • Resembles CLN2
      • Death between age 10-13 years
    • Juvenile phenotype
      • Visual loss or learning disabilities at age 5-7 years
      • Resembles CLN3 except epilepsy later but motor disability earlier
    • Adult phenotype
      • Starts in third decade
      • Psychiatric symptoms with progressive cognitive decline
      • Ataxia
      • Parkinsonism
      • Optic nerve atrophy
      • Alive in mid 50s
  • CLN2 or Jansky-Bielschowsky type or late infantile NCL
    • Late infantile phenotype
      • Onset between age 2-4 years
      • Epilepsy
      • Cognitive decline
      • Ataxia
      • Myoclonus
      • Extrapyramidal symptoms
      • Pyramidal symptoms
      • Blindness at age 4-6 years
      • Death before or in the second decade of life
    • Juvenile phenotype
      • Onset between age 6-8 years
      • Progressive cognitive decline
      • Seizures
      • Ataxia
      • Motor dysfunction
      • Variable vision loss
      • Survival up to fourth decade possible
  • CLN3 or Spielmeyer-Sjögren type or adult NCL
    • Classic phenotype
      • Progressive visual loss at age 4-7 years, with blindness within 2-10 years
      • Speech disturbance
      • Cognitive decline
      • Epilepsy
      • Psychiatric symptoms in 74% of patients, including
        social, thought, attention problems, somatic complaints, and aggression
      • Parkinsonism
      • Myoclonus
      • Sleep disturbance
      • Pyramidal symptoms
      • Cerebellar symptoms
      • Extrapyramidal symptoms
    • Protracted form - Only visual loss until age 40 years
  • CLN4 or Kufs disease or adult NCL - Symptoms usually at age 30 years but can present at age 11 years
    • Type A
      • Progressive myoclonic epilepsy
      • Dementia
      • Ataxia
      • Pyramidal symptoms
      • Extrapyramidal symptoms
    • Type B
      • Behavior abnormalities
      • Dementia
      • Motor dysfunction
      • Ataxia
      • Extrapyramidal symptoms
      • Suprabulbar symptoms
      • Onset maybe after age 50 years
  • CLN5 or Finnish variant late infantile NCL
    • Onset at age 4.5-7 years
    • Motor clumsiness
    • Concentration problems
    • Similar to CLN2 but slower course
    • Death in second or third decade
  • CLN6 or variant late infantile/early juvenile NCL (Lake Cavanagh disease)
    • Onset between age 18 months to 8 years
    • Visual loss
    • Seizures
    • Resembles CLN2
    • Loss of motor skills between age 4-10 years
    • Death in the second or third decade
  • CLN7 or Turkish variant late infantile NCL
  • CLN8 or Turkish variant late infantile NCL and Northern epilepsy
    • Turkish variant late infantile NCL
      • Onset at age 3-7.5 years
      • Progressive visual loss
      • Speech delay
      • Seizures
      • Intellectual decline
      • Myoclonus
      • Ataxia
    • Northern epilepsy
      • Epilepsy at age 5-10 years
      • Slight motor dysfunction
      • Slowly progressive mental retardation
      • May have reduced visual acuity
      • May survive to sixth decade
    • CLN9 juvenile NCL (CLN3) phenotype

Physical

Please see History section.

Causes

Please see Pathophysiology.

More on Neuronal Ceroid Lipofuscinoses

Overview: Neuronal Ceroid Lipofuscinoses
Differential Diagnoses & Workup: Neuronal Ceroid Lipofuscinoses
Treatment & Medication: Neuronal Ceroid Lipofuscinoses
Follow-up: Neuronal Ceroid Lipofuscinoses
References
[ CLOSE WINDOW ]

References

  1. Mole S. UCL. NCL Resource - A gateway for Batten disease. Available at http://www.ucl.ac.uk/ncl/index.shtml.

  2. Persaud-Sawin DA, Mousallem T, Wang C, Zucker A, Kominami E, Boustany RM. Neuronal ceroid lipofuscinosis: a common pathway?. Pediatr Res. Feb 2007;61(2):146-52. [Medline].

  3. Lyly A, von Schantz C, Salonen T, Kopra O, Saarela J, Jauhiainen M, et al. Glycosylation, transport, and complex formation of palmitoyl protein thioesterase 1 (PPT1)--distinct characteristics in neurons. BMC Cell Biol. Jun 12 2007;8:22. [Medline].

  4. Siintola E, Topcu M, Aula N, Lohi H, Minassian BA, Paterson AD, et al. The novel neuronal ceroid lipofuscinosis gene MFSD8 encodes a putative lysosomal transporter. Am J Hum Genet. Jul 2007;81(1):136-46. [Medline].

  5. Dyke JP, Voss HU, Sondhi D, Hackett NR, Worgall S, Heier LA, et al. Assessing disease severity in late infantile neuronal ceroid lipofuscinosis using quantitative MR diffusion-weighted imaging. AJNR Am J Neuroradiol. Aug 2007;28(7):1232-6. [Medline].

  6. Autti T, Hämäläinen J, Aberg L, Lauronen L, Tyynelä J, Van Leemput K. Thalami and corona radiata in juvenile NCL (CLN3): a voxel-based morphometric study. Eur J Neurol. Apr 2007;14(4):447-50. [Medline].

  7. Adams HR, Kwon J, Marshall FJ, de Blieck EA, Pearce DA, Mink JW. Neuropsychological symptoms of juvenile-onset batten disease: experiences from 2 studies. J Child Neurol. May 2007;22(5):621-7. [Medline].

  8. Anderson GW, Smith VV, Brooke I, Malone M, Sebire NJ. Diagnosis of neuronal ceroid lipofuscinosis (Batten disease) by electron microscopy in peripheral blood specimens. Ultrastruct Pathol. Sep-Oct 2006;30(5):373-8. [Medline].

  9. Worgall S, Kekatpure MV, Heier L, Ballon D, Dyke JP, Shungu D, et al. Neurological deterioration in late infantile neuronal ceroid lipofuscinosis. Neurology. Aug 7 2007;69(6):521-35. [Medline].

  10. Fowler DJ, Anderson G, Vellodi A, Malone M, Sebire NJ. Electron microscopy of chorionic villus samples for prenatal diagnosis of lysosomal storage disorders. Ultrastruct Pathol. Jan-Feb 2007;31(1):15-21. [Medline].

  11. Autti T, Raininko R, Vanhanen SL. Magnetic resonance techniques in neuronal ceroid lipofuscinoses and some other lysosomal diseases affecting the brain. Curr Opin Neurol. Dec 1997;10(6):519-24. [Medline].

  12. Backman ML, Santavuori PR, Aberg LE. Psychiatric symptoms of children and adolescents with juvenile neuronal ceroid lipofuscinosis. J Intellect Disabil Res. Jan 2005;49(Pt 1):25-32. [Medline].

  13. Bennett MJ, Hofmann SL. The neuronal ceroid-lipofuscinoses (Batten disease): a new class of lysosomal storage diseases. J Inherit Metab Dis. Jun 1999;22(4):535-44. [Medline].

  14. Crystal RG, Sondhi D, Hackett NR. Clinical protocol. Administration of a replication-deficient adeno-associated virus gene transfer vector expressing the human CLN2 cDNA to the brain of children with late infantile neuronal ceroid lipofuscinosis. Hum Gene Ther. Nov 2004;15(11):1131-54. [Medline].

  15. Das AK, Becerra CH, Yi W. Molecular genetics of palmitoyl-protein thioesterase deficiency in the U.S. J Clin Invest. Jul 15 1998;102(2):361-70. [Medline].

  16. Dooley TP, Probst P, Obermoeller RD. Phenol sulfotransferases: candidate genes for Batten disease. Am J Med Genet. Jun 5 1995;57(2):327-32. [Medline].

  17. Ezaki J, Kominami E. The intracellular location and function of proteins of neuronal ceroid lipofuscinoses. Brain Pathol. Jan 2004;14(1):77-85. [Medline].

  18. Ezaki J, Wolfe LS, Ishidoh K. Abnormal degradative pathway of mitochondrial ATP synthase subunit c in late infantile neuronal ceroid-lipofuscinosis (Batten disease). Am J Med Genet. Jun 5 1995;57(2):254-9. [Medline].

  19. Ezaki J, Wolfe LS, Ishidoh K. Lysosomal proteinosis based on decreased degradation of a specific protein, mitochondrial ATP synthase subunit C: Batten disease. Adv Exp Med Biol. 1996;389:121-8. [Medline].

  20. Gambardella A, Pasquinelli G, Cittadella R. Kufs'' disease presenting as late-onset epilepsia partialis continua. Neurology. Oct 1998;51(4):1180-2. [Medline].

  21. Gelot A, Maurage CA, Rodriguez D. In vivo diagnosis of Kufs'' disease by extracerebral biopsies. Acta Neuropathol (Berl). Jul 1998;96(1):102-8. [Medline].

  22. Goebel HH. The neuronal ceroid-lipofuscinoses. Semin Pediatr Neurol. Dec 1996;3(4):270-8. [Medline].

  23. Goebel HH, Sharp JD. The neuronal ceroid-lipofuscinoses. Recent advances. Brain Pathol. Jan 1998;8(1):151-62. [Medline].

  24. Goebel HH, Wisniewski KE. Current state of clinical and morphological features in human NCL. Brain Pathol. Jan 2004;14(1):61-9. [Medline].

  25. Griffey M, Macauley SL, Ogilvie JM. AAV2-mediated ocular gene therapy for infantile neuronal ceroid lipofuscinosis. Mol Ther. Sep 2005;12(3):413-21. [Medline].

  26. Hackett NR, Redmond DE, Sondhi D. Safety of Direct Administration of AAV2(CU)hCLN2, a Candidate Treatment for the Central Nervous System Manifestations of Late Infantile Neuronal Ceroid Lipofuscinosis, to the Brain of Rats and Nonhuman Primates. Hum Gene Ther. Nov 30 2005;[Medline].

  27. Haskell RE, Carr CJ, Pearce DA. Batten disease: evaluation of CLN3 mutations on protein localization and function. Hum Mol Genet. Mar 22 2000;9(5):735-44. [Medline].

  28. Hatonen T, Laakso ML, Heiskala H. Bright light suppresses melatonin in blind patients with neuronal ceroid-lipofuscinoses. Neurology. May 1998;50(5):1445-50. [Medline].

  29. Hobert JA, Dawson G. A novel role of the Batten disease gene CLN3: association with BMP synthesis. Biochem Biophys Res Commun. Jun 22 2007;358(1):111-6. [Medline].

  30. Jalanko A, Tyynelä J, Peltonen L. From genes to systems: new global strategies for the characterization of NCL biology. Biochim Biophys Acta. Oct 2006;1762(10):934-44. [Medline].

  31. Jarvela I, Sainio M, Rantamaki T. Biosynthesis and intracellular targeting of the CLN3 protein defective in Batten disease. Hum Mol Genet. Jan 1998;7(1):85-90. [Medline].

  32. Jolly RD. Comparative biology of the neuronal ceroid-lipofuscinoses (NCL): an overview. Am J Med Genet. Jun 5 1995;57(2):307-11. [Medline].

  33. Jolly RD, Palmer DN. The neuronal ceroid-lipofuscinoses (Batten disease): comparative aspects. Neuropathol Appl Neurobiol. Feb 1995;21(1):50-60. [Medline].

  34. Kohan R, de Halac IN, Tapia Anzolini V. 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. Clin Biochem. May 2005;38(5):492-4. [Medline].

  35. Kominami E, Ezaki J, Wolfe LS. New insight into lysosomal protein storage disease: delayed catabolism of ATP synthase subunit c in Batten disease. Neurochem Res. Nov 1995;20(11):1305-9. [Medline].

  36. Lonka L, Kyttala A, Ranta S, et al. The neuronal ceroid lipofuscinosis CLN8 membrane protein is a resident of the endoplasmic reticulum. Hum Mol Genet. Jul 1 2000;9(11):1691-7. [Medline].

  37. Mitchison HM, Lim MJ, Cooper JD. Selectivity and types of cell death in the neuronal ceroid lipofuscinoses. Brain Pathol. Jan 2004;14(1):86-96. [Medline].

  38. Mole SE. Batten''s disease: eight genes and still counting?. Lancet. Aug 7 1999;354(9177):443-5. [Medline].

  39. Mole SE. The genetic spectrum of human neuronal ceroid-lipofuscinoses. Brain Pathol. Jan 2004;14(1):70-6. [Medline].

  40. Mole SE, Mitchison HM, Munroe PB. Molecular basis of the neuronal ceroid lipofuscinoses: mutations in CLN1, CLN2, CLN3, and CLN5. Hum Mutat. 1999;14(3):199-215. [Medline].

  41. Molecular basis of NCL. Proceedings of the 10th international meeting of the NCL Foundation. 2005. Helsinki, Finland. Biochim Biophys Acta. Oct 2006;1762(10):849-953. [Medline].

  42. Munroe PB, Mitchison HM, O''Rawe AM. Spectrum of mutations in the Batten disease gene, CLN3. Am J Hum Genet. Aug 1997;61(2):310-6. [Medline].

  43. Munroe PB, Rapola J, Mitchison HM. Prenatal diagnosis of Batten''s disease. Lancet. Apr 13 1996;347(9007):1014-5. [Medline].

  44. Online Mendelian Inheritance in Man, OMIM (TM). Johns Hopkins University, Baltimore, MD. MIM Number: {162350}: {10/29/99}. [Full Text].

  45. Online Mendelian Inheritance in Man, OMIM (TM). Johns Hopkins University, Baltimore, MD. MIM Number: {204200}: {4/26/00}. [Full Text].

  46. Online Mendelian Inheritance in Man, OMIM (TM). Johns Hopkins University, Baltimore, MD. MIM Number: {204500}: {6/1/00}. [Full Text].

  47. Online Mendelian Inheritance in Man, OMIM (TM). Johns Hopkins University, Baltimore, MD. MIM Number: {256730}: {10/28/99}. [Full Text].

  48. Online Mendelian Inheritance in Man, OMIM (TM). Johns Hopkins University, Baltimore, MD. MIM Number: {256731}: {7/23/98}. [Full Text].

  49. Online Mendelian Inheritance in Man, OMIM (TM). Johns Hopkins University, Baltimore, MD. MIM Number: {600143}: {1/7/00}. [Full Text].

  50. Online Mendelian Inheritance in Man, OMIM (TM). Johns Hopkins University, Baltimore, MD. MIM Number: {600680}: {7/23/98}. [Full Text].

  51. Online Mendelian Inheritance in Man, OMIM (TM). Johns Hopkins University, Baltimore, MD. MIM Number: {600722}: {5/31/00}. [Full Text].

  52. Online Mendelian Inheritance in Man, OMIM (TM). Johns Hopkins University, Baltimore, MD. MIM Number: {601780}: {10/7/98}. [Full Text].

  53. Online Mendelian Inheritance in Man, OMIM (TM). Johns Hopkins University, Baltimore, MD. MIM Number: {204300}: {7/23/98}:. [Full Text].

  54. Opitz JM, Pullarkat RK, Reynold JF. Ceroid Lipofuscinoses: Batten Disease and Allied Disorders. Am J Med Genet. 1988;Supplement #5.

  55. Savukoski M, Klockars T, Holmberg V. CLN5, a novel gene encoding a putative transmembrane protein mutated in Finnish variant late infantile neuronal ceroid lipofuscinosis. Nat Genet. Jul 1998;19(3):286-8. [Medline].

  56. Schulz A, Dhar S, Rylova S. Impaired cell adhesion and apoptosis in a novel CLN9 Batten disease variant. Ann Neurol. Sep 2004;56(3):342-50. [Medline].

  57. Schulz A, Mousallem T, Venkataramani M. The CLN9 protein, a regulator of dihydroceramide synthase. J Biol Chem. Feb 3 2006;281(5):2784-94. [Medline].

  58. Siintola E, Topcu M, Aula N, Lohi H, Minassian BA, Paterson AD, et al. The novel neuronal ceroid lipofuscinosis gene MFSD8 encodes a putative lysosomal transporter. Am J Hum Genet. Jul 2007;81(1):136-46. [Medline].

  59. Sleat DE, Donnelly RJ, Lackland H. Association of mutations in a lysosomal protein with classical late- infantile neuronal ceroid lipofuscinosis. Science. Sep 19 1997;277(5333):1802-5. [Medline].

  60. Sondhi D, Peterson DA, Giannaris EL. AAV2-mediated CLN2 gene transfer to rodent and non-human primate brain results in long-term TPP-I expression compatible with therapy for LINCL. Gene Ther. Nov 2005;12(22):1618-32. [Medline].

  61. Tanner AJ, Dice JF. Batten disease and mitochondrial pathways of proteolysis. Biochem Mol Med. Feb 1996;57(1):1-9. [Medline].

  62. Taschner PE, de Vos N, Breuning MH. Rapid detection of the major deletion in the Batten disease gene CLN3 by allele specific PCR. J Med Genet. Nov 1997;34(11):955-6. [Medline].

  63. Walkley SU, March PA, Schroeder CE. Pathogenesis of brain dysfunction in Batten disease. Am J Med Genet. Jun 5 1995;57(2):196-203. [Medline].

  64. Warburton MJ, Bernardini F. Tripeptidyl-peptidase I deficiency in classical late-infantile neuronal ceroid lipofuscinosis brain tissue. Evidence for defective peptidase rather than proteinase activity [In Process Citation]. J Inherit Metab Dis. Mar 2000;23(2):145-54. [Medline].

  65. Weleber RG. The dystrophic retina in multisystem disorders: the electroretinogram in neuronal ceroid lipofuscinoses. Eye. 1998;12 ( Pt 3b):580-90. [Medline].

  66. Westermarck T, Aberg L, Santavuori P. Evaluation of the possible role of coenzyme Q10 and vitamin E in juvenile neuronal ceroid-lipofuscinosis (JNCL). Mol Aspects Med. 1997;18 Suppl:S259-62. [Medline].

  67. Wisniewski KE, Kida E. A new classification of neuronal ceroid lipofuscinoses based on the clinicopathologic and genetic information. 1998;44:577.

  68. Wisniewski KE, Zhong N, Kaczmarski W. Studies of atypical JNCL suggest overlapping with other NCL forms. Pediatr Neurol. Jan 1998;18(1):36-40. [Medline].

  69. Zhong N, Moroziewicz DN, Ju W, et al. Heterogeneity of late-infantile neuronal ceroid lipofuscinosis. Genet Med. Nov-Dec 2000;2(6):312-8. [Medline].

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

Batten disease, Parry's disease, Spielmeyer-Sjögren disease, Bielschowsky disease, Kufs disease, Santavuori-Haltia disease, neuronal ceroid lipofuscinoses, NCLs

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

Celia H Chang, MD, Associate Health Sciences Clinical Professor, Department of Neurology, University of California at Davis
Celia H Chang, MD is a member of the following medical societies: American Academy of Neurology and Child Neurology Society
Disclosure: Nothing to disclose.

Medical Editor

Beth A Pletcher, MD, Associate Professor, Co-Director of The Neurofibromatosis Center of New Jersey, Department of Pediatrics, University of Medicine and Dentistry of New Jersey
Beth A Pletcher, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics, American Medical Association, and American Society of Human Genetics
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Kenneth J Mack, MD, PhD, Senior Associate Consultant, Department of Child and Adolescent Neurology, Mayo Clinic
Kenneth J Mack, MD, PhD is a member of the following medical societies: American Academy of Neurology, Child Neurology Society, Phi Beta Kappa, and Society for Neuroscience
Disclosure: Nothing to disclose.

CME Editor

,, Kathy Roarty Placeholder
Disclosure: Nothing to disclose.

Chief Editor

Amy Kao, MD, Assistant Professor, Department of Pediatrics, Division of Pediatric Neurology, Department of Neurology, Oregon Health and Science University; Consulting Staff, Shriners Hospital for Children
Amy Kao, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, American Epilepsy Society, and Child Neurology Society
Disclosure: Nothing to disclose.

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.