Details of Disease

General Information of Disease (ID: DIS9A4K4)

Disease Name	Neuronal ceroid lipofuscinosis
Synonyms	neuronal ceroid lipofuscinosis; ceroid lipofuscinoses; NCL; hereditary ceroid lipofuscinosis
Disease Class	5C56: Lysosomal disease
Definition	A group of inherited progressive degenerative brain diseases characterized clinically by a decline of mental and other capacities, epilepsy, and vision loss through retinal degeneration, and histopathologically by intracellular accumulation of an autofluorescent material, ceroid lipofuscin, in the neuronal cells in the brain and in the retina.
Disease Hierarchy	DISXQRTX: Lysosomal lipid storage disorder DISPN7D2: Inherited neurodegenerative disorder DIS9A4K4: Neuronal ceroid lipofuscinosis
ICD Code	ICD-11 ICD-11: 5C56.1 ICD-10 ICD-10: E75.4
Disease Identifiers	MONDO ID MONDO_0016295 MESH ID D009472 UMLS CUI C0027877 MedGen ID 10326 Orphanet ID 216 SNOMED CT ID 42012007

Drug-Interaction Atlas (DIA) of This Disease

Drug-Interaction Atlas (DIA)

This Disease is Treated as An Indication in 1 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Cerliponase Alfa	DM0HAC8	Approved	Recombinant protein	[1]
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This Disease is Treated as An Indication in 1 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
BMN-190	DMG0PYA	Phase 2	NA	[2]
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Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 15 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
GRN	TT0LWE3	Limited	Genetic Variation	[3]
CTSD	TTPT2QI	moderate	Genetic Variation	[4]
CLCN3	TT8XNZ7	Strong	Biomarker	[5]
CLCN6	TTCJRDO	Strong	Biomarker	[6]
DPYSL2	TTZCW3T	Strong	Biomarker	[7]
PPP5C	TTTW7FJ	Strong	Genetic Variation	[8]
TARDBP	TT9RZ03	Strong	Biomarker	[9]
TRPM1	TTTDAI9	Strong	Biomarker	[10]
CLN3	TTORF9W	Definitive	Autosomal recessive	[11]
CLN6	TTJCOQ7	Definitive	Autosomal recessive	[11]
CTSD	TTPT2QI	Definitive	Autosomal recessive	[11]
CTSF	TTJOKD1	Definitive	Genetic Variation	[12]
GRN	TT4LM0E	Definitive	Autosomal recessive	[11]
PPT1	TTSQC14	Definitive	Autosomal recessive	[11]
TPP1	TTOVYPT	Definitive	Autosomal recessive	[11]
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⏷ Show the Full List of 15 DTT(s)

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC39A7	DTDQSAM	Strong	Biomarker	[13]
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This Disease Is Related to 23 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ARSG	OTT7TDW7	Limited	Biomarker	[14]
CAPN8	OTXTW2I4	Limited	Genetic Variation	[15]
FBXL3	OTDQ1QKV	Limited	CausalMutation	[16]
TBCK	OTP38GVK	Limited	Genetic Variation	[17]
ATP13A2	OTKWBUGK	Strong	Genetic Variation	[18]
ATP5MC1	OTOLSYOI	Strong	Biomarker	[19]
CAPN3	OTCHG3YK	Strong	Biomarker	[20]
KCTD7	OTRU3EOK	Strong	Genetic Variation	[21]
MAPK13	OT0W9GE7	Strong	Biomarker	[22]
POU4F1	OTMHYGWQ	Strong	Genetic Variation	[23]
PPT2	OTD5VJ9A	Strong	Biomarker	[24]
PRCD	OT64DNLW	Strong	Genetic Variation	[25]
PSAP	OTUOEKY7	Strong	Biomarker	[26]
TMEM106B	OTUWA6NW	Strong	Altered Expression	[27]
CLN3	OTDDKT8R	Definitive	Autosomal recessive	[11]
CLN5	OTY265P6	Definitive	Autosomal recessive	[11]
CLN6	OT91IAYT	Definitive	Autosomal recessive	[11]
CLN8	OT0D4CB5	Definitive	Autosomal recessive	[11]
CTSD	OTQZ36F3	Definitive	Autosomal recessive	[11]
GRN	OTXXSJ53	Definitive	Autosomal recessive	[11]
MFSD8	OT455EIC	Definitive	Autosomal recessive	[11]
PPT1	OTM3S4DE	Definitive	Autosomal recessive	[11]
TPP1	OT2LQ771	Definitive	Autosomal recessive	[11]
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⏷ Show the Full List of 23 DOT(s)

References

1	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2018
2	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
3	Genetic Regulation of Neuronal Progranulin Reveals a Critical Role for the Autophagy-Lysosome Pathway.J Neurosci. 2019 Apr 24;39(17):3332-3344. doi: 10.1523/JNEUROSCI.3498-17.2019. Epub 2019 Jan 29.
4	Enzyme replacement therapy with recombinant pro-CTSD (cathepsin D) corrects defective proteolysis and autophagy in neuronal ceroid lipofuscinosis.Autophagy. 2020 May;16(5):811-825. doi: 10.1080/15548627.2019.1637200. Epub 2019 Jul 16.
5	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.
6	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.
7	Protein product of CLN6 gene responsible for variant late-onset infantile neuronal ceroid lipofuscinosis interacts with CRMP-2.J Neurosci Res. 2009 Jul;87(9):2157-66. doi: 10.1002/jnr.22032.
8	Genotype-phenotype correlations in neuronal ceroid lipofuscinosis due to palmitoyl-protein thioesterase deficiency.Mol Genet Metab. 1999 Apr;66(4):234-9. doi: 10.1006/mgme.1999.2803.
9	Progranulin-mediated deficiency of cathepsin D results in FTD and NCL-like phenotypes in neurons derived from FTD patients.Hum Mol Genet. 2017 Dec 15;26(24):4861-4872. doi: 10.1093/hmg/ddx364.
10	Further delineation of eye manifestations in homozygous 15q13.3 microdeletions including TRPM1: a differential diagnosis of ceroid lipofuscinosis.Am J Med Genet A. 2014 Jun;164A(6):1537-44. doi: 10.1002/ajmg.a.36471. Epub 2014 Mar 25.
11	Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
12	Novel compound heterozygous mutations causing Kufs disease type B.Int J Neurosci. 2018 Jun;128(6):573-576. doi: 10.1080/00207454.2017.1403439. Epub 2017 Nov 22.
13	Deregulation of subcellular biometal homeostasis through loss of the metal transporter, Zip7, in a childhood neurodegenerative disorder.Acta Neuropathol Commun. 2014 Feb 28;2:25. doi: 10.1186/2051-5960-2-25.
14	Ataxia is the major neuropathological finding in arylsulfatase G-deficient mice: similarities and dissimilarities to Sanfilippo disease (mucopolysaccharidosis type III).Hum Mol Genet. 2015 Apr 1;24(7):1856-68. doi: 10.1093/hmg/ddu603. Epub 2014 Dec 1.
15	Batten disease: biochemical and molecular characterization revealing novel PPT1 and TPP1 gene mutations in Indian patients.BMC Neurol. 2018 Dec 12;18(1):203. doi: 10.1186/s12883-018-1206-1.
16	Proteolytic processing of the neuronal ceroid lipofuscinosis related lysosomal protein CLN5.Exp Cell Res. 2015 Oct 15;338(1):45-53. doi: 10.1016/j.yexcr.2015.08.021. Epub 2015 Sep 3.
17	Homozygous TBC1 domain-containing kinase (TBCK) mutation causes a novel lysosomal storage disease - a new type of neuronal ceroid lipofuscinosis (CLN15)?.Acta Neuropathol Commun. 2018 Dec 27;6(1):145. doi: 10.1186/s40478-018-0646-6.
18	ATP13A2 missense variant in Australian Cattle Dogs with late onset neuronal ceroid lipofuscinosis.Mol Genet Metab. 2019 May;127(1):95-106. doi: 10.1016/j.ymgme.2018.11.015. Epub 2019 Mar 27.
19	CLN6 p.I154del mutation causing late infantile neuronal ceroid lipofuscinosis in a large consanguineous Moroccan family.Indian J Pediatr. 2013 Aug;80(8):694-6. doi: 10.1007/s12098-012-0889-3. Epub 2012 Nov 22.
20	Characteristics of PPT1 and TPP1 enzymes in neuronal ceroid lipofuscinosis (NCL) 1 and 2 by dried blood spots (DBS) and leukocytes and their application to newborn screening.Mol Genet Metab. 2018 May;124(1):64-70. doi: 10.1016/j.ymgme.2018.03.007. Epub 2018 Mar 19.
21	Progressive myoclonus epilepsy and ceroidolipofuscinosis 14: The multifaceted phenotypic spectrum of KCTD7-related disorders.Eur J Med Genet. 2019 Dec;62(12):103591. doi: 10.1016/j.ejmg.2018.11.025. Epub 2018 Nov 27.
22	Endoplasmic reticulum stress-induced caspase-4 activation mediates apoptosis and neurodegeneration in INCL.Hum Mol Genet. 2006 Jun 1;15(11):1826-34. doi: 10.1093/hmg/ddl105. Epub 2006 Apr 27.
23	The Brn-3a transcription factor gene (POU4F1) maps close to the locus for the variant late infantile form of neuronal ceroid-lipofuscinosis.Cytogenet Cell Genet. 1996;74(3):225-6. doi: 10.1159/000134422.
24	Correlations between genotype, ultrastructural morphology and clinical phenotype in the neuronal ceroid lipofuscinoses.Neurogenetics. 2005 Sep;6(3):107-26. doi: 10.1007/s10048-005-0218-3. Epub 2005 Sep 28.
25	Electroretinograms in English setters with neuronal ceroid lipofuscinosis.Invest Ophthalmol Vis Sci. 1980 Jan;19(1):87-90.
26	Impaired prosaposin lysosomal trafficking in frontotemporal lobar degeneration due to progranulin mutations.Nat Commun. 2017 May 25;8:15277. doi: 10.1038/ncomms15277.
27	Common pathobiochemical hallmarks of progranulin-associated frontotemporal lobar degeneration and neuronal ceroid lipofuscinosis.Acta Neuropathol. 2014;127(6):845-60. doi: 10.1007/s00401-014-1262-6. Epub 2014 Mar 12.