MCID: CRD182
MIFTS: 45

Ceroid Lipofuscinosis, Neuronal, 10

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Metabolic diseases

Aliases & Classifications for Ceroid Lipofuscinosis, Neuronal, 10

MalaCards integrated aliases for Ceroid Lipofuscinosis, Neuronal, 10:

Name: Ceroid Lipofuscinosis, Neuronal, 10 54 71 13
Neuronal Ceroid Lipofuscinosis Due to Cathepsin D Deficiency 12 50 25 71 69
Neuronal Ceroid Lipofuscinosis 10 12 50 24 25 14
Cln10 12 50 25 71
Congenital Neuronal Ceroid Lipofuscinosis 25 56 71
Cathepsin D Deficiency 12 25 56
Cln10 Disease 24 25 56
Neuronal Ceroid Lipofuscinosis Cathepsin D-Deficient 12 71
Ceroid Lipofuscinosis Neuronal Cathepsin D-Deficient 50
Cathepsin D Deficient Neuronal Ceroid Lipofuscinosis 25
Ctsd-Related Neuronal Ceroid-Lipofuscinosis 24
Neuronal Ceroid Lipofuscinosis, Congenital 69
Ceroid Lipofuscinosis Neuronal 10 29
Cln10 Disease, Late Infantile 50
Cln10 Disease, Congenital 50
Cln10 Disease, Juvenile 50
Cln10 Disease, Adult 50
Congenital Ncl 56
Cathepsin D 13

Characteristics:

Orphanet epidemiological data:

56
congenital neuronal ceroid lipofuscinosis
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal; Age of death: early childhood;
cln10 disease
Inheritance: Autosomal recessive; Age of onset: All ages;

OMIM:

54
Inheritance:
autosomal recessive

Miscellaneous:
variable age at onset (range birth to teenage years)
patients with null mutations in (ctsd) show a more severe phenotype with onset at birth ('congenital ncl') and early death within days


HPO:

32
ceroid lipofuscinosis, neuronal, 10:
Mortality/Aging death in infancy
Onset and clinical course congenital onset
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Ceroid Lipofuscinosis, Neuronal, 10

Genetics Home Reference : 25 CLN10 disease is a severe disorder that primarily affects the nervous system. Individuals with this condition typically show signs and symptoms soon after birth. These signs and symptoms can include muscle rigidity, respiratory failure, and prolonged episodes of seizure activity that last several minutes (status epilepticus). It is likely that some affected individuals also have seizures before birth while in the womb. Infants with CLN10 disease have unusually small heads (microcephaly) with brains that may be less than half the normal size. There is a loss of brain cells in areas that coordinate movement (the cerebellum) and control thinking and emotions (the cerebral cortex). Nerve cells in the brain also lack a fatty substance called myelin, which protects them and promotes efficient transmission of nerve impulses. Infants with CLN10 disease often die hours to weeks after birth.

MalaCards based summary : Ceroid Lipofuscinosis, Neuronal, 10, also known as neuronal ceroid lipofuscinosis due to cathepsin d deficiency, is related to breast cancer and prostatitis, and has symptoms including seizures, microcephaly and respiratory insufficiency. An important gene associated with Ceroid Lipofuscinosis, Neuronal, 10 is CTSD (Cathepsin D), and among its related pathways/superpathways is Lysosome. The drug Menthol has been mentioned in the context of this disorder. Affiliated tissues include cerebellum, brain and cortex, and related phenotypes are behavior/neurological and nervous system

NIH Rare Diseases : 50 neuronal ceroid lipofuscinosis 10 (cln10-ncl) is a rare condition that affects the nervous system. signs and symptoms of the condition can develop any time from birth to adulthood and may include progressive dementia, seizures, lack of muscle coordination, and vision loss. cln10-ncl is caused by changes (mutations) in the ctsd gene and is inherited in an autosomal recessive manner. treatment options are limited to therapies that can help relieve some of the symptoms. last updated: 8/31/2015

UniProtKB/Swiss-Prot : 71 Ceroid lipofuscinosis, neuronal, 10: A form of neuronal ceroid lipofuscinosis with onset at birth or early childhood. Neuronal ceroid lipofuscinoses are progressive neurodegenerative, lysosomal storage diseases characterized by intracellular accumulation of autofluorescent liposomal material, and clinically by seizures, dementia, visual loss, and/or cerebral atrophy.

OMIM : 54
The neuronal ceroid lipofuscinoses (NCL; CLN) are a clinically and genetically heterogeneous group of neurodegenerative disorders characterized by the intracellular accumulation of autofluorescent lipopigment storage material in different patterns ultrastructurally. The clinical course includes progressive dementia, seizures, and progressive visual failure (Mole et al., 2005). For a discussion of genetic heterogeneity of neuronal ceroid lipofuscinosis, see CLN1 (256730). (610127)

Disease Ontology : 12 A neuronal ceroid lipofuscinosis that has material basis in homozygous or compound heterozygous mutation in the CTSD gene on chromosome 11p15.

Related Diseases for Ceroid Lipofuscinosis, Neuronal, 10

Diseases in the Neuronal Ceroid Lipofuscinosis family:

Ceroid Lipofuscinosis, Neuronal, 1 Ceroid Lipofuscinosis, Neuronal, 7
Ceroid Lipofuscinosis, Neuronal, 8 Ceroid Lipofuscinosis, Neuronal, 10
Ceroid Lipofuscinosis, Neuronal, 2 Ceroid Lipofuscinosis, Neuronal, 5
Ceroid Lipofuscinosis, Neuronal, 6 Ceroid Lipofuscinosis, Neuronal, 3
Ceroid Lipofuscinosis, Neuronal, 11 Ceroid Lipofuscinosis, Neuronal, 9
Neuronal Ceroid Lipofuscinosis 4a Adult Neuronal Ceroid Lipofuscinosis

Diseases related to Ceroid Lipofuscinosis, Neuronal, 10 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 26)
id Related Disease Score Top Affiliating Genes
1 breast cancer 10.6
2 prostatitis 10.2
3 colorectal cancer 10.1
4 adenocarcinoma 10.1
5 neuronitis 10.0
6 neuronal ceroid lipofuscinosis 9.9
7 cngb3-related stargardt disease 1 9.9 CLN6 DNAJC5
8 adult-onset nemaline myopathy 9.8 CLN6 DNAJC5
9 congenital vascular cavernous malformations 9.7 CLN6 DNAJC5
10 urinary schistosomiasis 9.7 CLN6 CLN8
11 neuronal ceroid-lipofuscinoses 9.6
12 blessig's cysts 9.5 CLN3 CLN5
13 esophagus liposarcoma 9.5 CLN6 CLN8
14 retinal degeneration, late-onset, autosomal dominant 9.5 CLN6 CLN8 DNAJC5
15 microcephaly 1, primary, autosomal recessive 9.4 CLN5 CLN6 CLN8
16 uterine corpus cancer 9.0 CLN3 CLN5 CLN6
17 diarrhea, chronic, with villous atrophy 9.0 CLN5 CLN6 CLN8 DNAJC5
18 macular dystrophy with central cone involvement 9.0 CLN5 CLN6 CLN8 DNAJC5
19 glans penis cancer 8.9 CLN5 CLN6 CLN8 DNAJC5
20 joubert syndrome 26 8.7 CLN3 CLN5 CLN6 CTSD
21 ceroid lipofuscinosis, neuronal, 1 7.8 CLN3 CLN5 CLN6 CLN8 CTSD DNAJC5
22 mental retardation, autosomal dominant 24 7.8 CLN3 CLN5 CLN6 CLN8 CTSD DNAJC5
23 spinocerebellar ataxia, autosomal recessive 7 7.8 CLN3 CLN5 CLN6 CLN8 CTSD DNAJC5
24 glanzmann thrombasthenia 7.8 CLN3 CLN5 CLN6 CLN8 CTSD DNAJC5
25 kashin-beck disease 7.8 CLN3 CLN5 CLN6 CLN8 CTSD DNAJC5
26 partial arterial retinal occlusion 7.8 CLN3 CLN5 CLN6 CLN8 CTSD DNAJC5

Graphical network of the top 20 diseases related to Ceroid Lipofuscinosis, Neuronal, 10:



Diseases related to Ceroid Lipofuscinosis, Neuronal, 10

Symptoms & Phenotypes for Ceroid Lipofuscinosis, Neuronal, 10

Symptoms via clinical synopsis from OMIM:

54

Neurologic- Central Nervous System:
ataxia
spasticity
seizures
rigidity
autofluorescent lipopigment in neurons
more
Head And Neck- Ears:
low-set ears

Respiratory:
apnea
respiratory failure

Head And Neck- Nose:
broad nasal bridge

Muscle Soft Tissue:
muscle biopsy shows angular atrophic fibers with granulovacuolar material (in some patients)
intracellular granular osmiophilic deposits

Laboratory- Abnormalities:
decrease or absence of cathepsin d (ctsd) protein immunostaining

Head And Neck- Head:
microcephaly

Head And Neck- Face:
sloping forehead

Head And Neck- Eyes:
retinitis pigmentosa
retinal atrophy
loss of vision, progressive

Skeletal- Skull:
overriding sutures
obliterated fontanelles

Neurologic- Peripheral Nervous System:
axonal sensory neuropathy (in some patients)


Clinical features from OMIM:

610127

Human phenotypes related to Ceroid Lipofuscinosis, Neuronal, 10:

56 32 (show all 26)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 seizures 56 32 hallmark (90%) Very frequent (99-80%) HP:0001250
2 microcephaly 56 32 hallmark (90%) Very frequent (99-80%) HP:0000252
3 respiratory insufficiency 56 32 hallmark (90%) Very frequent (99-80%) HP:0002093
4 ataxia 32 HP:0001251
5 intellectual disability, severe 32 HP:0010864
6 spasticity 32 HP:0001257
7 cerebral atrophy 32 HP:0002059
8 low-set ears 32 HP:0000369
9 sloping forehead 32 HP:0000340
10 rigidity 32 HP:0002063
11 apnea 32 HP:0002104
12 respiratory failure 32 HP:0002878
13 cerebellar atrophy 32 HP:0001272
14 wide nasal bridge 32 HP:0000431
15 rod-cone dystrophy 32 HP:0000510
16 status epilepticus 32 HP:0002133
17 death in infancy 56 Very frequent (99-80%)
18 mental deterioration 32 HP:0001268
19 visual loss 32 HP:0000572
20 retinal atrophy 32 HP:0001105
21 sensory axonal neuropathy 32 occasional (7.5%) HP:0003390
22 abnormality of metabolism/homeostasis 32 HP:0001939
23 intellectual disability, progressive 32 HP:0006887
24 neuronal loss in central nervous system 32 HP:0002529
25 premature closure of fontanelles 32 HP:0005458
26 increased neuronal autofluorescent lipopigment 32 HP:0002074

UMLS symptoms related to Ceroid Lipofuscinosis, Neuronal, 10:


ataxia, muscle rigidity, muscle spasticity, seizures

MGI Mouse Phenotypes related to Ceroid Lipofuscinosis, Neuronal, 10:

44
id Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.55 CLN6 CLN8 CTSD DNAJC5 CLN3
2 nervous system MP:0003631 9.43 CLN3 CLN5 CLN6 CLN8 CTSD DNAJC5
3 vision/eye MP:0005391 9.1 CLN3 CLN5 CLN6 CLN8 CTSD DNAJC5

Drugs & Therapeutics for Ceroid Lipofuscinosis, Neuronal, 10

Drugs for Ceroid Lipofuscinosis, Neuronal, 10 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


id Name Status Phase Clinical Trials Cas Number PubChem Id
1
Menthol Approved Phase 1 2216-51-5 16666

Interventional clinical trials:


id Name Status NCT ID Phase Drugs
1 AAVRh.10 Administered to Children With Late Infantile Neuronal Ceroid Lipofuscinosis Recruiting NCT01414985 Phase 1, Phase 2
2 Batten CLN6 Gene Therapy Recruiting NCT02725580 Phase 1, Phase 2 scAVV9.CB.CLN6
3 Safety Study of a Gene Transfer Vector (Rh.10) for Children With Late Infantile Neuronal Ceroid Lipofuscinosis Recruiting NCT01161576 Phase 1
4 Safety Study of a Gene Transfer Vector for Children With Late Infantile Neuronal Ceroid Lipofuscinosis Active, not recruiting NCT00151216 Phase 1

Search NIH Clinical Center for Ceroid Lipofuscinosis, Neuronal, 10

Genetic Tests for Ceroid Lipofuscinosis, Neuronal, 10

Genetic tests related to Ceroid Lipofuscinosis, Neuronal, 10:

id Genetic test Affiliating Genes
1 Ceroid Lipofuscinosis Neuronal 10 29
2 Cln10 Disease 24 CTSD

Anatomical Context for Ceroid Lipofuscinosis, Neuronal, 10

MalaCards organs/tissues related to Ceroid Lipofuscinosis, Neuronal, 10:

39
Cerebellum, Brain, Cortex

Publications for Ceroid Lipofuscinosis, Neuronal, 10

Variations for Ceroid Lipofuscinosis, Neuronal, 10

UniProtKB/Swiss-Prot genetic disease variations for Ceroid Lipofuscinosis, Neuronal, 10:

71
id Symbol AA change Variation ID SNP ID
1 CTSD p.Phe229Ile VAR_029362 rs121912789
2 CTSD p.Trp383Cys VAR_029363 rs121912790

ClinVar genetic disease variations for Ceroid Lipofuscinosis, Neuronal, 10:

6
id Gene Variation Type Significance SNP ID Assembly Location
1 CTSD NM_001909.4(CTSD): c.685T> A (p.Phe229Ile) single nucleotide variant Pathogenic rs121912789 GRCh37 Chromosome 11, 1778573: 1778573
2 CTSD NM_001909.4(CTSD): c.1149G> C (p.Trp383Cys) single nucleotide variant Pathogenic rs121912790 GRCh37 Chromosome 11, 1774823: 1774823
3 CTSD NM_001909.4(CTSD): c.764dupA (p.Tyr255Terfs) duplication Pathogenic rs786205105 GRCh37 Chromosome 11, 1776199: 1776199
4 CTSD NM_001909.4(CTSD): c.470C> T (p.Ser157Leu) single nucleotide variant Pathogenic rs587779409 GRCh37 Chromosome 11, 1780200: 1780200
5 CTSD NM_001909.4: c.486-12G> A single nucleotide variant Pathogenic
6 CTSD NM_001909.4(CTSD): c.446G> T (p.Gly149Val) single nucleotide variant Pathogenic rs797045137 GRCh38 Chromosome 11, 1758994: 1758994
7 CTSD NM_001909.4(CTSD): c.1196G> A (p.Arg399His) single nucleotide variant Pathogenic rs797045138 GRCh37 Chromosome 11, 1774776: 1774776
8 CTSD NM_001909.4(CTSD): c.686_688delTCT (p.Phe229del) deletion Likely pathogenic rs1057519591 GRCh37 Chromosome 11, 1778570: 1778572

Expression for Ceroid Lipofuscinosis, Neuronal, 10

Search GEO for disease gene expression data for Ceroid Lipofuscinosis, Neuronal, 10.

Pathways for Ceroid Lipofuscinosis, Neuronal, 10

Pathways related to Ceroid Lipofuscinosis, Neuronal, 10 according to GeneCards Suite gene sharing:

id Super pathways Score Top Affiliating Genes
1 10.89 CLN3 CLN5 CTSD

GO Terms for Ceroid Lipofuscinosis, Neuronal, 10

Cellular components related to Ceroid Lipofuscinosis, Neuronal, 10 according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 endoplasmic reticulum GO:0005783 9.46 CLN3 CLN5 CLN6 CLN8
2 synaptic vesicle GO:0008021 9.32 CLN3 DNAJC5
3 melanosome GO:0042470 9.26 CTSD DNAJC5
4 lysosome GO:0005764 9.13 CLN3 CLN5 CTSD
5 lysosomal membrane GO:0005765 8.8 CLN3 CLN5 DNAJC5

Biological processes related to Ceroid Lipofuscinosis, Neuronal, 10 according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 negative regulation of neuron apoptotic process GO:0043524 9.4 CLN3 DNAJC5
2 cholesterol metabolic process GO:0008203 9.37 CLN6 CLN8
3 lysosome organization GO:0007040 9.32 CLN3 CLN6
4 negative regulation of proteolysis GO:0045861 9.26 CLN3 CLN8
5 ceramide metabolic process GO:0006672 9.16 CLN3 CLN8
6 lysosomal lumen acidification GO:0007042 9.13 CLN3 CLN5 CLN6
7 protein catabolic process GO:0030163 9.02 CLN3 CLN5 CLN6 CLN8 CTSD

Sources for Ceroid Lipofuscinosis, Neuronal, 10

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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