MCID: CRD182
MIFTS: 44

Ceroid Lipofuscinosis, Neuronal, 10

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

Aliases & Classifications for Ceroid Lipofuscinosis, Neuronal, 10

MalaCards integrated aliases for Ceroid Lipofuscinosis, Neuronal, 10:

Name: Ceroid Lipofuscinosis, Neuronal, 10 53 71 13
Neuronal Ceroid Lipofuscinosis Due to Cathepsin D Deficiency 53 12 49 24 71 69
Cln10 53 12 49 24 71
Neuronal Ceroid Lipofuscinosis 10 12 49 24 14
Cathepsin D Deficiency 12 49 24 55
Congenital Neuronal Ceroid Lipofuscinosis 24 55 71
Neuronal Ceroid Lipofuscinosis Cathepsin D-Deficient 12 71
Cln10 Disease 24 55
Ceroid Lipofuscinosis, Neuronal, Cathepsin D-Deficient 53
Ceroid Lipofuscinosis Neuronal Cathepsin D-Deficient 49
Cathepsin D Deficient Neuronal Ceroid Lipofuscinosis 24
Neuronal Ceroid Lipofuscinosis, Congenital 69
Ceroid Lipofuscinosis Neuronal 10 28
Cln10 Disease, Late Infantile 49
Cln10 Disease, Congenital 49
Cln10 Disease, Juvenile 49
Cln10 Disease, Adult 49
Congenital Ncl 55
Cathepsin D 13

Characteristics:

Orphanet epidemiological data:

55
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:

53
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:

31
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 : 49 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. Last updated: 11/9/2017

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 seizures, respiratory insufficiency and microcephaly. 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 nervous system and vision/eye

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 : 24 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 : 53 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 : 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.

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 20)
# Related Disease Score Top Affiliating Genes
1 ceroid lipofuscinosis, neuronal, 1 27.3 CLN3 CLN5 CLN6 CLN8 CTSD KCTD7
2 neuronal ceroid lipofuscinosis 27.3 CLN3 CLN5 CLN6 CLN8 CTSD KCTD7
3 breast cancer 10.4
4 alzheimer disease 10.4
5 prostatitis 10.2
6 adenocarcinoma 10.2
7 colorectal cancer 10.2
8 neuronitis 9.9
9 ceroid lipofuscinosis, neuronal, 13 9.5 CLN5 CLN8 KCTD7
10 progressive myoclonus epilepsy 9.5 CLN6 KCTD7
11 ceroid lipofuscinosis, neuronal, 9 9.5 CLN5 CLN6 CLN8
12 ceroid lipofuscinosis, neuronal, 8, northern epilepsy variant 9.4 CLN5 CLN6 CLN8
13 ceroid lipofuscinosis, neuronal, 7 9.3 CLN5 CLN6 CLN8
14 visual epilepsy 9.1 CLN5 CLN6 CLN8 KCTD7
15 ceroid storage disease 9.0 CLN3 CLN5 CLN6 CLN8
16 ceroid lipofuscinosis, neuronal, 3 9.0 CLN3 CLN5 CLN6 CTSD
17 lipid storage disease 8.9 CLN3 CLN5 CLN6 CLN8
18 ceroid lipofuscinosis, neuronal, 2 8.7 CLN3 CLN5 CLN6 CLN8 CTSD
19 neuronal ceroid-lipofuscinoses 8.6 CLN3 CLN5 CLN6 CLN8 CTSD
20 ceroid lipofuscinosis, neuronal, 11 8.3 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:

53
Neurologic Central Nervous System:
ataxia
seizures
spasticity
rigidity
status epilepticus
more
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

Head And Neck Ears:
low-set ears

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:

55 31 (show all 26)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 seizures 55 31 hallmark (90%) Very frequent (99-80%) HP:0001250
2 respiratory insufficiency 55 31 hallmark (90%) Very frequent (99-80%) HP:0002093
3 microcephaly 55 31 hallmark (90%) Very frequent (99-80%) HP:0000252
4 ataxia 31 HP:0001251
5 low-set ears 31 HP:0000369
6 spasticity 31 HP:0001257
7 wide nasal bridge 31 HP:0000431
8 intellectual disability, severe 31 HP:0010864
9 abnormality of metabolism/homeostasis 31 HP:0001939
10 death in infancy 55 Very frequent (99-80%)
11 sensory axonal neuropathy 31 occasional (7.5%) HP:0003390
12 apnea 31 HP:0002104
13 intellectual disability, progressive 31 HP:0006887
14 rigidity 31 HP:0002063
15 visual loss 31 HP:0000572
16 respiratory failure 31 HP:0002878
17 mental deterioration 31 HP:0001268
18 cerebellar atrophy 31 HP:0001272
19 sloping forehead 31 HP:0000340
20 status epilepticus 31 HP:0002133
21 rod-cone dystrophy 31 HP:0000510
22 cerebral atrophy 31 HP:0002059
23 neuronal loss in central nervous system 31 HP:0002529
24 premature closure of fontanelles 31 HP:0005458
25 retinal atrophy 31 HP:0001105
26 increased neuronal autofluorescent lipopigment 31 HP:0002074

UMLS symptoms related to Ceroid Lipofuscinosis, Neuronal, 10:


seizures, muscle spasticity, muscle rigidity, ataxia, apnea

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

43
# 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 CTSD CLN3 CLN5 CLN6 CLN8

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 28 CTSD

Anatomical Context for Ceroid Lipofuscinosis, Neuronal, 10

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

38
Brain, Cerebellum, Cortex

Publications for Ceroid Lipofuscinosis, Neuronal, 10

Articles related to Ceroid Lipofuscinosis, Neuronal, 10:

(show all 14)
# Title Authors Year
1
Early infantile neuronal ceroid lipofuscinosis (CLN10 disease) associated with a novel mutation in CTSD. ( 27072142 )
2016
2
Murine cathepsin D deficiency is associated with dysmyelination/myelin disruption and accumulation of cholesteryl esters in the brain. ( 19845830 )
2010
3
Genetic modifiers of degeneration in the cathepsin D deficient Drosophila model for neuronal ceroid lipofuscinosis. ( 19761846 )
2009
4
Synaptic changes in the thalamocortical system of cathepsin D-deficient mice: a model of human congenital neuronal ceroid-lipofuscinosis. ( 18091563 )
2008
5
Cathepsin D deficiency induces persistent neurodegeneration in the absence of Bax-dependent apoptosis. ( 17314303 )
2007
6
Altered regulation of phosphatidylinositol 3-kinase signaling in cathepsin D-deficient brain. ( 17297299 )
2007
7
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
8
Cathepsin D deficiency and NCL/Batten disease: there's more to death than apoptosis. ( 17495518 )
2007
9
Cathepsin D deficiency is associated with a human neurodegenerative disorder. ( 16685649 )
2006
10
Cathepsin D deficiency underlies congenital human neuronal ceroid- lipofuscinosis. ( 16670177 )
2006
11
Proteolytic degradation of glutamate decarboxylase mediates disinhibition of hippocampal CA3 pyramidal cells in cathepsin D-deficient mice. ( 15992379 )
2005
12
Cathepsin D-deficient Drosophila recapitulate the key features of neuronal ceroid lipofuscinoses. ( 15837574 )
2005
13
Congenital ovine neuronal ceroid lipofuscinosis--a cathepsin D deficiency with increased levels of the inactive enzyme. ( 11589006 )
2001
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:

71
# 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
# 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:

# 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
16 ExPASy
18 FMA
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29 HGMD
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42 MESH via Orphanet
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58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
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70 UMLS via Orphanet
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