MCID: CRD182
MIFTS: 43

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 57 75 13
Neuronal Ceroid Lipofuscinosis Due to Cathepsin D Deficiency 57 12 53 25 75 73
Cln10 57 12 53 25 75
Neuronal Ceroid Lipofuscinosis 10 12 53 25 15
Cathepsin D Deficiency 12 53 25 59
Congenital Neuronal Ceroid Lipofuscinosis 25 59 75
Neuronal Ceroid Lipofuscinosis Cathepsin D-Deficient 12 75
Ceroid Lipofuscinosis Neuronal 10 29 6
Cln10 Disease 25 59
Ceroid Lipofuscinosis, Neuronal, Cathepsin D-Deficient 57
Ceroid Lipofuscinosis Neuronal Cathepsin D-Deficient 53
Cathepsin D Deficient Neuronal Ceroid Lipofuscinosis 25
Neuronal Ceroid Lipofuscinosis, Congenital 73
Lipofuscinosis, Ceroid, Neuronal, Type 10 40
Cln10 Disease, Late Infantile 53
Cln10 Disease, Congenital 53
Cln10 Disease, Juvenile 53
Cln10 Disease, Adult 53
Congenital Ncl 59
Cathepsin D 13

Characteristics:

Orphanet epidemiological data:

59
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:

57
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

NIH Rare Diseases : 53 Neuronal ceroid lipofuscinosis 10 (CLN10 disease) is a type of neuronal ceroid lipofuscinosis (NCL), a group of severe diseases that affect the nervous system. Signs and symptoms of CLN10 usually appear soon after birth. They may include muscle stiffness, respiratory failure, and seizures that last several minutes (status epilepticus). Infants with CLN10 disease have a small brain and small head (microcephaly). They also have problems controlling their movements. The areas of the brain involved in thinking and emotions are also severely affected. Sadly, infants with CLN10 disease often do not survive longer than hours or weeks after birth. In some cases, people with CLN10 disease do not develop symptoms until later in infancy, childhood, or adulthood. Symptoms in these cases may be more gradual and include ataxia, loss of speech and vision, and problems with memory and thinking (cognitive impairment). The lifespan of people diagnosed after early infancy is also shortened, but varies based on when their symptoms began. CLN10 disease is caused by changes (mutations) in the CTSD gene and inheritance is autosomal recessive. If the disease-causing genetic change completely prevents the CLN10 protein (cathepsin D) from being made, the infant will be born with the severe type. If however, some working CLN2 protein is made, the person will develop either the late infantile, juvenile, or adult type. At this time, there are no effective treatment options for CLN10 disease. Therefore, therapy is aimed at easing symptoms and improving quality of life (palliative care).Please note: Batten disease originally referred specifically to the juvenile and most common form of NCL, now known as CLN3. However, the term Batten disease is increasingly used to describe all forms of NCL. All types of NCL also belong to a larger group of diseases known as lysosomal storage disorders.

MalaCards based summary : Ceroid Lipofuscinosis, Neuronal, 10, also known as neuronal ceroid lipofuscinosis due to cathepsin d deficiency, is related to ceroid lipofuscinosis, neuronal, 1 and neuronal ceroid lipofuscinosis, and has symptoms including apnea, ataxia and muscle rigidity. An important gene associated with Ceroid Lipofuscinosis, Neuronal, 10 is CTSD (Cathepsin D), and among its related pathways/superpathways is Lysosome. Affiliated tissues include brain, cerebellum and cortex, and related phenotypes are microcephaly and seizures

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

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.

OMIM : 57 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)

UniProtKB/Swiss-Prot : 75 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.

Related Diseases for Ceroid Lipofuscinosis, Neuronal, 10

Diseases in the Neuronal Ceroid Lipofuscinosis family:

Ceroid Lipofuscinosis, Neuronal, 4b, Autosomal Dominant Ceroid Lipofuscinosis, Neuronal, 3
Ceroid Lipofuscinosis, Neuronal, 4a, Autosomal Recessive Ceroid Lipofuscinosis, Neuronal, 2
Ceroid Lipofuscinosis, Neuronal, 1 Ceroid Lipofuscinosis, Neuronal, 5
Ceroid Lipofuscinosis, Neuronal, 8 Ceroid Lipofuscinosis, Neuronal, 6
Ceroid Lipofuscinosis, Neuronal, 9 Ceroid Lipofuscinosis, Neuronal, 10
Ceroid Lipofuscinosis, Neuronal, 7 Ceroid Lipofuscinosis, Neuronal, 11
Ceroid Lipofuscinosis, Neuronal, 13 Adult Neuronal Ceroid Lipofuscinosis

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

(show all 21)
# Related Disease Score Top Affiliating Genes
1 ceroid lipofuscinosis, neuronal, 1 25.8 CLN3 CLN5 CLN6 CLN8 CTSD KCTD7
2 neuronal ceroid lipofuscinosis 25.8 CLN3 CLN5 CLN6 CLN8 CTSD KCTD7
3 breast cancer 10.6
4 alzheimer disease 10.4
5 prostatitis 10.2
6 colorectal cancer 10.2
7 adenocarcinoma 10.2
8 neuronitis 9.9
9 cerebral atrophy 9.5 CLN6 CLN8
10 ceroid lipofuscinosis, neuronal, 13 9.3 CLN5 CLN8 KCTD7
11 ceroid lipofuscinosis, neuronal, 9 9.3 CLN5 CLN6 CLN8
12 progressive myoclonus epilepsy 9.2 CLN6 KCTD7
13 ceroid lipofuscinosis, neuronal, 8, northern epilepsy variant 9.2 CLN5 CLN6 CLN8
14 ceroid lipofuscinosis, neuronal, 7 9.1 CLN5 CLN6 CLN8
15 ceroid lipofuscinosis, neuronal, 3 8.9 CLN3 CLN5 CTSD
16 ceroid storage disease 8.3 CLN3 CLN5 CLN6 CLN8
17 lipid storage disease 8.3 CLN3 CLN5 CLN6 CLN8
18 neuronal ceroid-lipofuscinoses 7.9 CLN3 CLN5 CLN6 CLN8 CTSD
19 visual epilepsy 7.8 CLN3 CLN5 CLN6 CLN8 KCTD7
20 ceroid lipofuscinosis, neuronal, 11 7.3 CLN3 CLN5 CLN6 CLN8 CTSD KCTD7
21 ceroid lipofuscinosis, neuronal, 2 7.3 CLN3 CLN5 CLN6 CLN8 CTSD KCTD7

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:

57
Head And Neck Ears:
low-set ears

Head And Neck Head:
microcephaly

Head And Neck Face:
sloping forehead

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

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

Neurologic Central Nervous System:
seizures
ataxia
spasticity
rigidity
status epilepticus
more
Respiratory:
apnea
respiratory failure

Head And Neck Nose:
broad nasal bridge

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:

59 32 (show all 26)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 microcephaly 59 32 hallmark (90%) Very frequent (99-80%) HP:0000252
2 seizures 59 32 hallmark (90%) Very frequent (99-80%) HP:0001250
3 respiratory insufficiency 59 32 hallmark (90%) Very frequent (99-80%) HP:0002093
4 death in infancy 59 Very frequent (99-80%)
5 sloping forehead 32 HP:0000340
6 low-set ears 32 HP:0000369
7 wide nasal bridge 32 HP:0000431
8 rod-cone dystrophy 32 HP:0000510
9 visual loss 32 HP:0000572
10 retinal atrophy 32 HP:0001105
11 ataxia 32 HP:0001251
12 spasticity 32 HP:0001257
13 mental deterioration 32 HP:0001268
14 cerebellar atrophy 32 HP:0001272
15 abnormality of metabolism/homeostasis 32 HP:0001939
16 cerebral atrophy 32 HP:0002059
17 rigidity 32 HP:0002063
18 increased neuronal autofluorescent lipopigment 32 HP:0002074
19 apnea 32 HP:0002104
20 status epilepticus 32 HP:0002133
21 neuronal loss in central nervous system 32 HP:0002529
22 respiratory failure 32 HP:0002878
23 sensory axonal neuropathy 32 occasional (7.5%) HP:0003390
24 premature closure of fontanelles 32 HP:0005458
25 intellectual disability, progressive 32 HP:0006887
26 intellectual disability, severe 32 HP:0010864

UMLS symptoms related to Ceroid Lipofuscinosis, Neuronal, 10:


apnea, ataxia, muscle rigidity, muscle spasticity, seizures

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

46
# Description MGI Source Accession Score Top Affiliating Genes
1 nervous system MP:0003631 9.35 CLN3 CLN5 CLN6 CLN8 CTSD
2 vision/eye MP:0005391 9.02 CLN3 CLN5 CLN6 CLN8 CTSD

Drugs & Therapeutics for Ceroid Lipofuscinosis, Neuronal, 10

Search Clinical Trials , NIH Clinical Center for Ceroid Lipofuscinosis, Neuronal, 10

Genetic Tests for Ceroid Lipofuscinosis, Neuronal, 10

Genetic tests related to Ceroid Lipofuscinosis, Neuronal, 10:

# Genetic test Affiliating Genes
1 Ceroid Lipofuscinosis Neuronal 10 29 CTSD

Anatomical Context for Ceroid Lipofuscinosis, Neuronal, 10

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

41
Brain, Cerebellum, Cortex

Publications for Ceroid Lipofuscinosis, Neuronal, 10

Articles related to Ceroid Lipofuscinosis, Neuronal, 10:

(show all 14)
# Title Authors Year
1
Murine cathepsin D deficiency is associated with dysmyelination/myelin disruption and accumulation of cholesteryl esters in the brain. ( 19845830 )
2010
2
Genetic modifiers of degeneration in the cathepsin D deficient Drosophila model for neuronal ceroid lipofuscinosis. ( 19761846 )
2009
3
Synaptic changes in the thalamocortical system of cathepsin D-deficient mice: a model of human congenital neuronal ceroid-lipofuscinosis. ( 18091563 )
2008
4
In vivo MRI reveals the dynamics of pathological changes in the brains of cathepsin D-deficient mice and correlates changes in manganese-enhanced MRI with microglial activation. ( 17451907 )
2007
5
Cathepsin D deficiency induces persistent neurodegeneration in the absence of Bax-dependent apoptosis. ( 17314303 )
2007
6
Cathepsin D deficiency and NCL/Batten disease: there's more to death than apoptosis. ( 17495518 )
2007
7
Altered regulation of phosphatidylinositol 3-kinase signaling in cathepsin D-deficient brain. ( 17297299 )
2007
8
Cathepsin D deficiency underlies congenital human neuronal ceroid- lipofuscinosis. ( 16670177 )
2006
9
Cathepsin D deficiency is associated with a human neurodegenerative disorder. ( 16685649 )
2006
10
Cathepsin D-deficient Drosophila recapitulate the key features of neuronal ceroid lipofuscinoses. ( 15837574 )
2005
11
Proteolytic degradation of glutamate decarboxylase mediates disinhibition of hippocampal CA3 pyramidal cells in cathepsin D-deficient mice. ( 15992379 )
2005
12
Congenital ovine neuronal ceroid lipofuscinosis--a cathepsin D deficiency with increased levels of the inactive enzyme. ( 11589006 )
2001
13
Cathepsin D deficiency induces lysosomal storage with ceroid lipofuscin in mouse CNS neurons. ( 10995834 )
2000
14
Proteolysis of IGFBPs by cathepsin D in vitro and in cathepsin D-deficient mice. ( 8817669 )
1995

Variations for Ceroid Lipofuscinosis, Neuronal, 10

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

75
# 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
(show all 17)
# 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.685T> A (p.Phe229Ile) single nucleotide variant Pathogenic rs121912789 GRCh38 Chromosome 11, 1757343: 1757343
3 CTSD NM_001909.4(CTSD): c.1149G> C (p.Trp383Cys) single nucleotide variant Pathogenic rs121912790 GRCh37 Chromosome 11, 1774823: 1774823
4 CTSD NM_001909.4(CTSD): c.1149G> C (p.Trp383Cys) single nucleotide variant Pathogenic rs121912790 GRCh38 Chromosome 11, 1753593: 1753593
5 CTSD NM_001909.4(CTSD): c.764dupA (p.Tyr255Terfs) duplication Pathogenic rs786205105 GRCh37 Chromosome 11, 1776199: 1776199
6 CTSD NM_001909.4(CTSD): c.764dupA (p.Tyr255Terfs) duplication Pathogenic rs786205105 GRCh38 Chromosome 11, 1754969: 1754969
7 CTSD NM_001909.4(CTSD): c.470C> T (p.Ser157Leu) single nucleotide variant Pathogenic rs587779409 GRCh37 Chromosome 11, 1780200: 1780200
8 CTSD NM_001909.4(CTSD): c.470C> T (p.Ser157Leu) single nucleotide variant Pathogenic rs587779409 GRCh38 Chromosome 11, 1758970: 1758970
9 CTSD NM_001909.4: c.486-12G> A single nucleotide variant Pathogenic
10 CTSD NM_001909.4(CTSD): c.446G> T (p.Gly149Val) single nucleotide variant Pathogenic rs797045137 GRCh38 Chromosome 11, 1758994: 1758994
11 CTSD NM_001909.4(CTSD): c.446G> T (p.Gly149Val) single nucleotide variant Pathogenic rs797045137 GRCh37 Chromosome 11, 1780224: 1780224
12 CTSD NM_001909.4(CTSD): c.1196G> A (p.Arg399His) single nucleotide variant Pathogenic rs797045138 GRCh37 Chromosome 11, 1774776: 1774776
13 CTSD NM_001909.4(CTSD): c.1196G> A (p.Arg399His) single nucleotide variant Pathogenic rs797045138 GRCh38 Chromosome 11, 1753546: 1753546
14 CTSD NM_001909.4(CTSD): c.828-17G> A single nucleotide variant Benign rs78735768 GRCh37 Chromosome 11, 1775385: 1775385
15 CTSD NM_001909.4(CTSD): c.828-17G> A single nucleotide variant Benign rs78735768 GRCh38 Chromosome 11, 1754155: 1754155
16 CTSD NM_001909.4(CTSD): c.686_688delTCT (p.Phe229del) deletion Likely pathogenic rs1057519591 GRCh37 Chromosome 11, 1778570: 1778572
17 CTSD NM_001909.4(CTSD): c.686_688delTCT (p.Phe229del) deletion Likely pathogenic rs1057519591 GRCh38 Chromosome 11, 1757340: 1757342

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:

# 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:

# Name GO ID Score Top Affiliating Genes
1 endoplasmic reticulum GO:0005783 9.26 CLN3 CLN5 CLN6 CLN8
2 lysosome GO:0005764 8.8 CLN3 CLN5 CTSD

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

# Name GO ID Score Top Affiliating Genes
1 cholesterol metabolic process GO:0008203 9.37 CLN6 CLN8
2 lysosome organization GO:0007040 9.32 CLN3 CLN6
3 negative regulation of proteolysis GO:0045861 9.26 CLN3 CLN8
4 ceramide metabolic process GO:0006672 9.16 CLN3 CLN8
5 lysosomal lumen acidification GO:0007042 9.13 CLN3 CLN5 CLN6
6 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
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
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36 IUPHAR
37 KEGG
38 LifeMap
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42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
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58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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