Details of Disease

General Information of Disease (ID: DISI3RIL)

• Disease Name: Late infantile neuronal ceroid lipofuscinosis
• Synonyms: dollinger-Bielschowsky type neuronal ceroid lipofuscinosis; Bielschowsky-jansky type neuronal ceroid lipofuscinosis; amaurotic idiocy early juvenile type; amaurotic idiocy late infantile type; Bielschowsky-jansky disease; amaurotic idiocy, early juvenile type; dollinger-Bielschowsky syndrome; amaurotic idiocy, late infantile type; Jansky-Bielschowsky disease; LINCL; late infantile NCL; late-infantile neuronal ceroid lipofuscinosis
• Definition: A genetically heterogeneous group of neuronal ceroid lipofuscinoses (NCLs) typically characterized by onset during infancy or early childhood with decline of mental and motor capacities, epilepsy, and vision loss through retinal degeneration.
• Disease Hierarchy:
  DIS6QM6U: Lysosomal storage disease
  DISI3RIL: Late infantile neuronal ceroid lipofuscinosis
• Disease Identifiers:
  MONDO ID: MONDO_0015674
  MESH ID: D009472
  UMLS CUI: C0022340
  MedGen ID: 9589
  Orphanet ID: 168491
  SNOMED CT ID: 14637005

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 9 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
CLCN3	TT8XNZ7	Limited	Biomarker	[1]
CLCN6	TTCJRDO	Limited	Biomarker	[2]
CTSD	TTPT2QI	Limited	Biomarker	[3]
TPP1	TTOVYPT	Limited	Biomarker	[4]
CLN3	TTORF9W	Strong	Biomarker	[5]
CLN6	TTJCOQ7	Strong	Genetic Variation	[6]
NCL	TTK1V5Q	Strong	Genetic Variation	[6]
PPT1	TTSQC14	Strong	Biomarker	[7]
TPP2	TTQ7R2V	Definitive	Biomarker	[8]

This Disease Is Related to 6 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
CLN5	OTY265P6	moderate	Biomarker	[9]
ATP13A2	OTKWBUGK	Strong	Biomarker	[10]
ATP5MC1	OTOLSYOI	Strong	Biomarker	[11]
CLN8	OT0D4CB5	Strong	Genetic Variation	[12]
MFSD8	OT455EIC	Strong	Genetic Variation	[13]
ACD	OTC54EPO	Definitive	Altered Expression	[14]

References

• [1] ClC-3 chloride channels facilitate endosomal acidification and chloride accumulation.J Biol Chem. 2005 Jan 14;280(2):1241-7. doi: 10.1074/jbc.M407030200. Epub 2004 Oct 25.
• [2] Lysosomal storage disease upon disruption of the neuronal chloride transport protein ClC-6.Proc Natl Acad Sci U S A. 2006 Sep 12;103(37):13854-9. doi: 10.1073/pnas.0606137103. Epub 2006 Sep 1.
• [3] Involvement of two different cell death pathways in retinal atrophy of cathepsin D-deficient mice.Mol Cell Neurosci. 2003 Feb;22(2):146-61. doi: 10.1016/s1044-7431(03)00035-6.
• [4] Validity of a rapid and simple fluorometric tripeptidyl peptidase 1 (TPP1) assay using dried blood specimens to diagnose CLN2 disease.Clin Chim Acta. 2019 May;492:69-71. doi: 10.1016/j.cca.2019.02.010. Epub 2019 Feb 13.
• [5] Proteomic Analysis of Brain and Cerebrospinal Fluid from the Three Major Forms of Neuronal Ceroid Lipofuscinosis Reveals Potential Biomarkers.J Proteome Res. 2017 Oct 6;16(10):3787-3804. doi: 10.1021/acs.jproteome.7b00460. Epub 2017 Aug 28.
• [6] Novel mutations in CLN6 cause late-infantile neuronal ceroid lipofuscinosis without visual impairment in two unrelated patients.Mol Genet Metab. 2019 Feb;126(2):188-195. doi: 10.1016/j.ymgme.2018.12.001. Epub 2018 Dec 3.
• [7] The novel Cln1(R151X) mouse model of infantile neuronal ceroid lipofuscinosis (INCL) for testing nonsense suppression therapy.Hum Mol Genet. 2015 Jan 1;24(1):185-96. doi: 10.1093/hmg/ddu428. Epub 2014 Sep 8.
• [8] A critical tryptophan and Ca2+ in activation and catalysis of TPPI, the enzyme deficient in classic late-infantile neuronal ceroid lipofuscinosis.PLoS One. 2010 Aug 3;5(8):e11929. doi: 10.1371/journal.pone.0011929.
• [9] CLN5 mutations are frequent in juvenile and late-onset non-Finnish patients with NCL. Neurology. 2010 Feb 16;74(7):565-71. doi: 10.1212/WNL.0b013e3181cff70d.
• [10] Characterization of cellular protective effects of ATP13A2/PARK9 expression and alterations resulting from pathogenic mutants. J Neurosci Res. 2012 Dec;90(12):2306-16. doi: 10.1002/jnr.23112. Epub 2012 Jul 30.
• [11] Abnormal degradative pathway of mitochondrial ATP synthase subunit c in late infantile neuronal ceroid-lipofuscinosis (Batten disease).Am J Med Genet. 1995 Jun 5;57(2):254-9. doi: 10.1002/ajmg.1320570229.
• [12] Novel missense mutation in CLN8 in late infantile neuronal ceroid lipofuscinosis: The first report of a CLN8 mutation in Japan.Brain Dev. 2016 Mar;38(3):341-5. doi: 10.1016/j.braindev.2015.09.008. Epub 2015 Oct 9.
• [13] Rett-like onset in late-infantile neuronal ceroid lipofuscinosis (CLN7) caused by compound heterozygous mutation in the MFSD8 gene and review of the literature data on clinical onset signs.Eur J Paediatr Neurol. 2015 Jan;19(1):78-86. doi: 10.1016/j.ejpn.2014.07.008. Epub 2014 Aug 7.
• [14] 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. 2005 Nov;12(22):1618-32. doi: 10.1038/sj.gt.3302549.