CLN4A
MCID: CRD226
MIFTS: 38

Ceroid Lipofuscinosis, Neuronal, 4a, Autosomal Recessive (CLN4A)

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

Aliases & Classifications for Ceroid Lipofuscinosis, Neuronal, 4a, Autosomal Recessive

MalaCards integrated aliases for Ceroid Lipofuscinosis, Neuronal, 4a, Autosomal Recessive:

Name: Ceroid Lipofuscinosis, Neuronal, 4a, Autosomal Recessive 58
Cln4a 58 12 76
Ceroid Lipofuscinosis, Neuronal, Kufs Type, Adult Onset 58 13
Autosomal Recessive Neuronal Ceroid Lipofuscinosis 4a 12 54
Adult Neuronal Ceroid Lipofuscinosis 76 74
Ceroid Lipofuscinosis, Neuronal, 4a 76
Neuronal Ceroid Lipofuscinosis 4a 12
Kufs Disease Autosomal Recessive 76
Cln6 Disease Kufs Type a 76
Cln4a Disease 60
Kufs Disease 76

Characteristics:

Orphanet epidemiological data:

60
cln4a disease
Inheritance: Autosomal recessive; Age of onset: Adult;

OMIM:

58
Inheritance:
autosomal recessive

Miscellaneous:
onset in adulthood (third to fourth decade)
type a characterized by progressive myoclonic epilepsy
type b characterized by dementia, motor disturbances, and facial dyskinesia
for similar autosomal dominant form, see


HPO:

33
ceroid lipofuscinosis, neuronal, 4a, autosomal recessive:
Onset and clinical course adult onset
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Ceroid Lipofuscinosis, Neuronal, 4a, Autosomal Recessive

OMIM : 58 Adult-onset neuronal ceroid lipofuscinosis, also known as Kufs disease, is a neurodegenerative disorder without retinal involvement. There are 2 overlapping phenotypes: type A, characterized by progressive myoclonic epilepsy, and type B, characterized by dementia and a variety of motor-system signs (summary by Arsov et al., 2011). In general, 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. The ultrastructural pattern of lipopigment in CLN4 comprises a mixed pattern of 'granular,' 'curvilinear,' and 'fingerprint' profiles (Mole et al., 2005). For a general phenotypic description and a discussion of genetic heterogeneity of CLN, see CLN1 (256730). (204300)

MalaCards based summary : Ceroid Lipofuscinosis, Neuronal, 4a, Autosomal Recessive, also known as cln4a, is related to adult neuronal ceroid lipofuscinosis and ceroid lipofuscinosis, neuronal, 4b, autosomal dominant, and has symptoms including seizures, myoclonus and abnormality of extrapyramidal motor function. An important gene associated with Ceroid Lipofuscinosis, Neuronal, 4a, Autosomal Recessive is CLN6 (CLN6 Transmembrane ER Protein). The drugs Cysteamine and Acetylcysteine have been mentioned in the context of this disorder. Affiliated tissues include eye and retina, and related phenotypes are depressivity and seizures

Disease Ontology : 12 A neuronal ceroid lipofuscinosis that is characterized by adult-onset of progressive dementia, seizures, and progressive visual failure and lipopigment patterns with mixed combinations of 'granular,' 'curvilinear,' and 'fingerprint' profiles and has material basis in homozygous or compound heterozygous mutation in the CLN6 gene on chromosome 15q23.

UniProtKB/Swiss-Prot : 76 Ceroid lipofuscinosis, neuronal, 4A: An adult-onset neuronal ceroid lipofuscinosis. 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. CLN4A has no visual involvement and is characterized by progressive myoclonic epilepsy.

Related Diseases for Ceroid Lipofuscinosis, Neuronal, 4a, Autosomal Recessive

Graphical network of the top 20 diseases related to Ceroid Lipofuscinosis, Neuronal, 4a, Autosomal Recessive:



Diseases related to Ceroid Lipofuscinosis, Neuronal, 4a, Autosomal Recessive

Symptoms & Phenotypes for Ceroid Lipofuscinosis, Neuronal, 4a, Autosomal Recessive

Human phenotypes related to Ceroid Lipofuscinosis, Neuronal, 4a, Autosomal Recessive:

33 (show all 15)
# Description HPO Frequency HPO Source Accession
1 depressivity 33 HP:0000716
2 seizures 33 HP:0001250
3 ataxia 33 HP:0001251
4 myoclonus 33 HP:0001336
5 dementia 33 HP:0000726
6 abnormality of extrapyramidal motor function 33 HP:0002071
7 cerebral atrophy 33 HP:0002059
8 visual hallucinations 33 HP:0002367
9 leukoencephalopathy 33 HP:0002352
10 auditory hallucinations 33 HP:0008765
11 granular osmiophilic deposits (grod) in cells 33 HP:0003657
12 increased neuronal autofluorescent lipopigment 33 HP:0002074
13 curvilinear intracellular accumulation of autofluorescent lipopigment storage material 33 HP:0003205
14 fingerprint intracellular accumulation of autofluorescent lipopigment storage material 33 HP:0003208
15 rectilinear intracellular accumulation of autofluorescent lipopigment storage material 33 HP:0003226

Symptoms via clinical synopsis from OMIM:

58
Neurologic Central Nervous System:
seizures
myoclonus
dementia
cerebral atrophy
extrapyramidal signs
more
Laboratory Abnormalities:
granular osmiophilic deposits (grod) in cells resulting in 'fingerprint' profiles ultrastructurally
granular osmiophilic deposits (grod) in cells resulting in 'curvilinear' profiles ultrastructurally
granular osmiophilic deposits (grod) in cells resulting in 'rectilinear' profiles ultrastructurally

Neurologic Behavioral Psychiatric Manifestations:
depression
behavioral changes
auditory and visual hallucinations

Clinical features from OMIM:

204300

UMLS symptoms related to Ceroid Lipofuscinosis, Neuronal, 4a, Autosomal Recessive:


seizures, myoclonus, abnormality of extrapyramidal motor function, cerebellar ataxia

Drugs & Therapeutics for Ceroid Lipofuscinosis, Neuronal, 4a, Autosomal Recessive

Drugs for Ceroid Lipofuscinosis, Neuronal, 4a, Autosomal Recessive (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 31)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Cysteamine Approved, Investigational Phase 4 60-23-1 6058
2
Acetylcysteine Approved, Investigational Phase 4 616-91-1 12035
3 Antioxidants Phase 4
4 Expectorants Phase 4
5 N-monoacetylcystine Phase 4
6 Antidotes Phase 4
7 Antiviral Agents Phase 4
8 Free Radical Scavengers Phase 4
9 Anti-Infective Agents Phase 4,Phase 2
10 Respiratory System Agents Phase 4
11 Protective Agents Phase 4
12
Busulfan Approved, Investigational Phase 2, Phase 3 55-98-1 2478
13
Methylprednisolone hemisuccinate Approved Phase 2, Phase 3 2921-57-5
14
Methylprednisolone Approved, Vet_approved Phase 2, Phase 3 83-43-2 6741
15
Cyclophosphamide Approved, Investigational Phase 2, Phase 3 6055-19-2, 50-18-0 2907
16
Prednisolone phosphate Approved, Vet_approved Phase 2, Phase 3 302-25-0
17
Prednisolone Approved, Vet_approved Phase 2, Phase 3 50-24-8 5755
18
Prednisolone hemisuccinate Experimental Phase 2, Phase 3 2920-86-7
19 Antilymphocyte Serum Phase 2, Phase 3
20 Antirheumatic Agents Phase 2, Phase 3
21 Methylprednisolone Acetate Phase 2, Phase 3
22 Immunologic Factors Phase 2, Phase 3
23 Alkylating Agents Phase 2, Phase 3
24 Immunosuppressive Agents Phase 2, Phase 3
25 Antineoplastic Agents, Alkylating Phase 2, Phase 3
26 Prednisolone acetate Phase 2, Phase 3
27
Mycophenolic acid Approved Phase 2 24280-93-1 446541
28
Omeprazole Approved, Investigational, Vet_approved Phase 2 73590-58-6 4594
29 Anti-Bacterial Agents Phase 2
30 Antibiotics, Antitubercular Phase 2
31 Antitubercular Agents Phase 2

Interventional clinical trials:

(show all 27)
# Name Status NCT ID Phase Drugs
1 Cystagon to Treat Infantile Neuronal Ceroid Lipofuscinosis Completed NCT00028262 Phase 4 Cystagon
2 Stem Cell Transplant for Inborn Errors of Metabolism Completed NCT00176904 Phase 2, Phase 3 Busulfan, Cyclophosphamide, Antithymocyte Globulin
3 A Phase 1/2 Open-Label Dose-Escalation Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Efficacy of Intracerebroventricular BMN 190 in Patients With Late-Infantile Neuronal Ceroid Lipofuscinosis (CLN2) Disease Completed NCT01907087 Phase 1, Phase 2
4 Cellcept for Treatment of Juvenile Neuronal Ceroid Lipofuscinosis Completed NCT01399047 Phase 2 Mycophenolate mofetil;Liquid Placebo
5 Gene Transfer Study of AAV9-CLN3 for Treatment NCL Type 3 Recruiting NCT03770572 Phase 1, Phase 2
6 AAVRh.10 Administered to Children With Late Infantile Neuronal Ceroid Lipofuscinosis Active, not recruiting NCT01414985 Phase 1, Phase 2
7 Batten CLN6 Gene Therapy Active, not recruiting NCT02725580 Phase 1, Phase 2 scAVV9.CB.CLN6
8 A Multicenter, Multinational, Extension Study to Evaluate the Long-Term Efficacy and Safety of BMN 190 in Patients With CLN2 Disease Active, not recruiting NCT02485899 Phase 1, Phase 2
9 A Safety, Tolerability, and Efficacy Study of Intracerebroventricular BMN 190 in Pediatric Patients < 18 Years of Age With CLN2 Disease Enrolling by invitation NCT02678689 Phase 2
10 Study of HuCNS-SC Cells in Patients With Infantile or Late Infantile Neuronal Ceroid Lipofuscinosis (NCL) Completed NCT00337636 Phase 1 Medication to suppress the immune system
11 UCB Transplant of Inherited Metabolic Diseases With Administration of Intrathecal UCB Derived Oligodendrocyte-Like Cells Recruiting NCT02254863 Phase 1
12 Safety Study of a Gene Transfer Vector for Children With Late Infantile Neuronal Ceroid Lipofuscinosis Active, not recruiting NCT00151216 Phase 1
13 Safety Study of a Gene Transfer Vector (Rh.10) for Children With Late Infantile Neuronal Ceroid Lipofuscinosis (LINCL) Active, not recruiting NCT01161576 Phase 1
14 Human Placental-Derived Stem Cell Transplantation Active, not recruiting NCT01586455 Phase 1 Human Placental Derived Stem Cell
15 Safety and Efficacy Study of HuCNS-SC in Subjects With Neuronal Ceroid Lipofuscinosis Withdrawn NCT01238315 Phase 1
16 Neuronal Ceroid Lipofuscinosis and Associated Sleep Abnormalities Completed NCT01966757
17 Genotype - Phenotype Correlations of LINCL Completed NCT00151268
18 Investigations of Juvenile Neuronal Ceroid Lipofuscinosis Recruiting NCT03307304
19 Clinical and Neuropsychological Investigations in Batten Disease Recruiting NCT01873924
20 Natural History of Neuronal Ceroid Lipofuscinosis, Batten's CLN6 Diseae Recruiting NCT03285425
21 A Natural History Study of Late Infantile Variant CLN7 And CLN5 Disease Recruiting NCT03822650
22 Examining Developmental Outcomes of Children Diagnosed With CLN2 Disease Recruiting NCT03862274
23 Genetic Characterization of Movement Disorders and Dementias Recruiting NCT02014246
24 Longitudinal Study of Neurodegenerative Disorders Recruiting NCT03333200
25 Inherited Retinal Degenerative Disease Registry Recruiting NCT02435940
26 Genotype-Phenotype Correlations of Late Infantile Neuronal Ceroid Lipofuscinosis Active, not recruiting NCT01035424
27 Collection of Cerebrospinal Fluid in Healthy Children Terminated NCT01698229

Search NIH Clinical Center for Ceroid Lipofuscinosis, Neuronal, 4a, Autosomal Recessive

Genetic Tests for Ceroid Lipofuscinosis, Neuronal, 4a, Autosomal Recessive

Anatomical Context for Ceroid Lipofuscinosis, Neuronal, 4a, Autosomal Recessive

MalaCards organs/tissues related to Ceroid Lipofuscinosis, Neuronal, 4a, Autosomal Recessive:

42
Eye, Retina

Publications for Ceroid Lipofuscinosis, Neuronal, 4a, Autosomal Recessive

Articles related to Ceroid Lipofuscinosis, Neuronal, 4a, Autosomal Recessive:

(show all 23)
# Title Authors Year
1
Diagnosis and misdiagnosis of adult neuronal ceroid lipofuscinosis (Kufs disease). ( 27412140 )
2016
2
Expression profile of a Caenorhabditis elegans model of adult neuronal ceroid lipofuscinosis reveals down regulation of ubiquitin E3 ligase components. ( 26395859 )
2015
3
Oligomerization of Cysteine String Protein alpha mutants causing adult neuronal ceroid lipofuscinosis. ( 25064588 )
2014
4
Same gene, surprising difference: adult neuronal ceroid lipofuscinosis linked to CLN6, mutated in variant late-infantile form. ( 21819394 )
2011
5
Exome-sequencing confirms DNAJC5 mutations as cause of adult neuronal ceroid-lipofuscinosis. ( 22073189 )
2011
6
Electroencephalography in autosomal dominant adult neuronal ceroid lipofuscinosis. ( 19699676 )
2009
7
Adult neuronal ceroid lipofuscinosis caused by deficiency in palmitoyl protein thioesterase 1. ( 17261688 )
2007
8
Autosomal dominant adult neuronal ceroid lipofuscinosis: a novel form of NCL with granular osmiophilic deposits without palmitoyl protein thioesterase 1 deficiency. ( 14655761 )
2003
9
Autosomal dominant adult neuronal ceroid lipofuscinosis: parkinsonism due to both striatal and nigral dysfunction. ( 12112194 )
2002
10
Adult neuronal ceroid lipofuscinosis with palmitoyl-protein thioesterase deficiency: first adult-onset patients of a childhood disease. ( 11506414 )
2001
11
Pre- and postnatal enzyme analysis for infantile, late infantile and adult neuronal ceroid lipofuscinosis (CLN1 and CLN2). ( 11588995 )
2001
12
Adult neuronal ceroid lipofuscinosis (Kufs' disease) in two siblings of an Irish family. ( 14606583 )
2000
13
Ultrastructure of the retina in adult neuronal ceroid lipofuscinosis. ( 9831759 )
1998
14
Adult neuronal ceroid lipofuscinosis with clinical findings consistent with a butterfly glioma. Case report. ( 9452242 )
1998
15
Diagnostic (clinical and morphological) criteria for adult neuronal ceroid-lipofuscinosis (Kufs' disease), HA'pital de la SalpActriA"re 'AFM Institut de Myologie', Paris, France, 5 December 1996. ( 9223136 )
1997
16
Adult neuronal ceroid-lipofuscinosis--personal observations. ( 9246375 )
1997
17
Adult neuronal ceroid lipofuscinosis presenting with psychiatric symptoms: a case report. ( 8175244 )
1993
18
Pathoarchitectonic pattern of iso- and allocortical lesions in juvenile and adult neuronal ceroid-lipofuscinosis. ( 8411975 )
1993
19
Adult neuronal ceroid-lipofuscinosis. ( 2663281 )
1989
20
A case of adult neuronal ceroid-lipofuscinosis with the appearance of membranous cytoplasmic bodies localized in the spinal anterior horn. ( 3033977 )
1987
21
An autopsy case of adult neuronal ceroid lipofuscinosis. ( 3599568 )
1986
22
Morphologic studies on adult neuronal-ceroid lipofuscinosis (NCL). ( 7168921 )
1982
23
Adult neuronal ceroid lipofuscinosis (Kufs' disease). A sporadic case. ( 7302734 )
1981

Variations for Ceroid Lipofuscinosis, Neuronal, 4a, Autosomal Recessive

UniProtKB/Swiss-Prot genetic disease variations for Ceroid Lipofuscinosis, Neuronal, 4a, Autosomal Recessive:

76
# Symbol AA change Variation ID SNP ID
1 CLN6 p.Arg6Thr VAR_065834 rs154774636
2 CLN6 p.Leu47Phe VAR_065836 rs154774635
3 CLN6 p.Leu67Pro VAR_065837 rs154774633
4 CLN6 p.Asn77Lys VAR_065838 rs154774641
5 CLN6 p.Arg103Gln VAR_065839 rs154774634
6 CLN6 p.Arg149His VAR_065840 rs154774638
7 CLN6 p.Phe238Thr VAR_065841

ClinVar genetic disease variations for Ceroid Lipofuscinosis, Neuronal, 4a, Autosomal Recessive:

6 (show all 12)
# Gene Variation Type Significance SNP ID Assembly Location
1 CLN6 NM_017882.2(CLN6): c.53C> T (p.Ala18Val) single nucleotide variant Conflicting interpretations of pathogenicity rs547125345 GRCh37 Chromosome 15, 68521870: 68521870
2 CLN6 NM_017882.2(CLN6): c.53C> T (p.Ala18Val) single nucleotide variant Conflicting interpretations of pathogenicity rs547125345 GRCh38 Chromosome 15, 68229532: 68229532
3 CLN6 NM_017882.2(CLN6): c.923G> C (p.Ser308Thr) single nucleotide variant Conflicting interpretations of pathogenicity rs143578698 GRCh37 Chromosome 15, 68500491: 68500491
4 CLN6 NM_017882.2(CLN6): c.923G> C (p.Ser308Thr) single nucleotide variant Conflicting interpretations of pathogenicity rs143578698 GRCh38 Chromosome 15, 68208153: 68208153
5 CLN6 NM_017882.2(CLN6): c.200T> C (p.Leu67Pro) single nucleotide variant Pathogenic rs154774633 GRCh37 Chromosome 15, 68506725: 68506725
6 CLN6 NM_017882.2(CLN6): c.200T> C (p.Leu67Pro) single nucleotide variant Pathogenic rs154774633 GRCh38 Chromosome 15, 68214387: 68214387
7 CLN6 NM_017882.2(CLN6): c.308G> A (p.Arg103Gln) single nucleotide variant Uncertain significance rs154774634 GRCh37 Chromosome 15, 68504191: 68504191
8 CLN6 NM_017882.2(CLN6): c.308G> A (p.Arg103Gln) single nucleotide variant Uncertain significance rs154774634 GRCh38 Chromosome 15, 68211853: 68211853
9 CLN6 NM_017882.2(CLN6): c.139C> T (p.Leu47Phe) single nucleotide variant Uncertain significance rs154774635 GRCh37 Chromosome 15, 68510933: 68510933
10 CLN6 NM_017882.2(CLN6): c.139C> T (p.Leu47Phe) single nucleotide variant Uncertain significance rs154774635 GRCh38 Chromosome 15, 68218595: 68218595
11 CLN6 NM_017882.2(CLN6): c.17G> C (p.Arg6Thr) single nucleotide variant Pathogenic rs154774636 GRCh37 Chromosome 15, 68521906: 68521906
12 CLN6 NM_017882.2(CLN6): c.17G> C (p.Arg6Thr) single nucleotide variant Pathogenic rs154774636 GRCh38 Chromosome 15, 68229568: 68229568

Expression for Ceroid Lipofuscinosis, Neuronal, 4a, Autosomal Recessive

Search GEO for disease gene expression data for Ceroid Lipofuscinosis, Neuronal, 4a, Autosomal Recessive.

Pathways for Ceroid Lipofuscinosis, Neuronal, 4a, Autosomal Recessive

GO Terms for Ceroid Lipofuscinosis, Neuronal, 4a, Autosomal Recessive

Sources for Ceroid Lipofuscinosis, Neuronal, 4a, Autosomal Recessive

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