MCID: CRD226
MIFTS: 36

Ceroid Lipofuscinosis, Neuronal, 4a, Autosomal Recessive

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Metabolic 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 57
Cln4a 57 12 75
Ceroid Lipofuscinosis, Neuronal, Kufs Type, Adult Onset 57 13
Autosomal Recessive Neuronal Ceroid Lipofuscinosis 4a 12 53
Adult Neuronal Ceroid Lipofuscinosis 75 73
Ceroid Lipofuscinosis, Neuronal, 4a 75
Neuronal Ceroid Lipofuscinosis 4a 12
Kufs Disease Autosomal Recessive 75
Cln6 Disease Kufs Type a 75
Cln4a Disease 59
Kufs Disease 75

Characteristics:

Orphanet epidemiological data:

59
cln4a disease
Inheritance: Autosomal recessive; Age of onset: Adult;

OMIM:

57
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:

32
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 : 57 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 (Mole et al., 2005). 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 cerebellar ataxia, myoclonus and seizures. An important gene associated with Ceroid Lipofuscinosis, Neuronal, 4a, Autosomal Recessive is CLN6 (CLN6, Transmembrane ER Protein). The drugs Acetylcysteine and Cysteamine have been mentioned in the context of this disorder. Affiliated tissues include retina, and related phenotypes are depressivity and dementia

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 : 75 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

Symptoms via clinical synopsis from OMIM:

57
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

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

32 (show all 15)
# Description HPO Frequency HPO Source Accession
1 depressivity 32 HP:0000716
2 dementia 32 HP:0000726
3 seizures 32 HP:0001250
4 ataxia 32 HP:0001251
5 myoclonus 32 HP:0001336
6 cerebral atrophy 32 HP:0002059
7 abnormality of extrapyramidal motor function 32 HP:0002071
8 increased neuronal autofluorescent lipopigment 32 HP:0002074
9 leukoencephalopathy 32 HP:0002352
10 visual hallucinations 32 HP:0002367
11 curvilinear intracellular accumulation of autofluorescent lipopigment storage material 32 HP:0003205
12 fingerprint intracellular accumulation of autofluorescent lipopigment storage material 32 HP:0003208
13 rectilinear intracellular accumulation of autofluorescent lipopigment storage material 32 HP:0003226
14 granular osmiophilic deposits (grod) in cells 32 HP:0003657
15 auditory hallucinations 32 HP:0008765

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


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

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
Acetylcysteine Approved, Investigational Phase 4 616-91-1 12035
2
Cysteamine Approved, Investigational Phase 4 60-23-1 6058
3 Antidotes Phase 4
4 Anti-Infective Agents Phase 4,Phase 2
5 Antioxidants Phase 4
6 Antiviral Agents Phase 4
7 Expectorants Phase 4
8 N-monoacetylcystine Phase 4
9 Protective Agents Phase 4
10 Respiratory System Agents Phase 4
11
Busulfan Approved, Investigational Phase 2, Phase 3 55-98-1 2478
12
Cyclophosphamide Approved, Investigational Phase 2, Phase 3 50-18-0, 6055-19-2 2907
13
Methylprednisolone Approved, Vet_approved Phase 2, Phase 3 83-43-2 6741
14
Prednisolone Approved, Vet_approved Phase 2, Phase 3 50-24-8 5755
15 Alkylating Agents Phase 2, Phase 3
16 Antilymphocyte Serum Phase 2, Phase 3
17 Antineoplastic Agents, Alkylating Phase 2, Phase 3
18 Antirheumatic Agents Phase 2, Phase 3
19 Immunosuppressive Agents Phase 2, Phase 3
20 Methylprednisolone acetate Phase 2, Phase 3
21 Methylprednisolone Hemisuccinate Phase 2, Phase 3
22 Prednisolone acetate Phase 2, Phase 3
23 Prednisolone hemisuccinate Phase 2, Phase 3
24 Prednisolone phosphate Phase 2, Phase 3
25
Mycophenolate mofetil Approved, Investigational Phase 2 128794-94-5 5281078
26
Mycophenolic acid Approved Phase 2 24280-93-1 446541
27
Omeprazole Approved, Investigational, Vet_approved Phase 2 73590-58-6 4594
28 Anti-Bacterial Agents Phase 2
29 Antibiotics, Antitubercular Phase 2
30 Antitubercular Agents Phase 2
31
Menthol Approved Phase 1 2216-51-5 16666

Interventional clinical trials:

(show all 24)
# 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 Batten CLN6 Gene Therapy Recruiting NCT02725580 Phase 1, Phase 2 scAVV9.CB.CLN6
6 AAVRh.10 Administered to Children With Late Infantile Neuronal Ceroid Lipofuscinosis Active, not recruiting NCT01414985 Phase 1, Phase 2
7 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
8 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
9 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
10 UCB Transplant of Inherited Metabolic Diseases With Administration of Intrathecal UCB Derived Oligodendrocyte-Like Cells Recruiting NCT02254863 Phase 1
11 Safety Study of a Gene Transfer Vector for Children With Late Infantile Neuronal Ceroid Lipofuscinosis Active, not recruiting NCT00151216 Phase 1
12 Safety Study of a Gene Transfer Vector (Rh.10) for Children With Late Infantile Neuronal Ceroid Lipofuscinosis (LINCL) Active, not recruiting NCT01161576 Phase 1
13 Human Placental-Derived Stem Cell Transplantation Active, not recruiting NCT01586455 Phase 1 Human Placental Derived Stem Cell
14 Safety and Efficacy Study of HuCNS-SC in Subjects With Neuronal Ceroid Lipofuscinosis Withdrawn NCT01238315 Phase 1
15 Neuronal Ceroid Lipofuscinosis and Associated Sleep Abnormalities Completed NCT01966757
16 Genotype - Phenotype Correlations of LINCL Completed NCT00151268
17 Investigations of Juvenile Neuronal Ceroid Lipofuscinosis Recruiting NCT03307304
18 Clinical and Neuropsychological Investigations in Batten Disease Recruiting NCT01873924
19 Natural History of Neuronal Ceroid Lipofuscinosis, Batten's CLN6 Diseae Recruiting NCT03285425
20 Genetic Characterization of Movement Disorders and Dementias Recruiting NCT02014246
21 Longitudinal Study of Neurodegenerative Disorders Recruiting NCT03333200
22 Inherited Retinal Degenerative Disease Registry Recruiting NCT02435940
23 Genotype-Phenotype Correlations of Late Infantile Neuronal Ceroid Lipofuscinosis Active, not recruiting NCT01035424
24 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:

41
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:

75
# 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.200T> C (p.Leu67Pro) single nucleotide variant Pathogenic rs154774633 GRCh37 Chromosome 15, 68506725: 68506725
2 CLN6 NM_017882.2(CLN6): c.200T> C (p.Leu67Pro) single nucleotide variant Pathogenic rs154774633 GRCh38 Chromosome 15, 68214387: 68214387
3 CLN6 NM_017882.2(CLN6): c.308G> A (p.Arg103Gln) single nucleotide variant Pathogenic rs154774634 GRCh37 Chromosome 15, 68504191: 68504191
4 CLN6 NM_017882.2(CLN6): c.308G> A (p.Arg103Gln) single nucleotide variant Pathogenic rs154774634 GRCh38 Chromosome 15, 68211853: 68211853
5 CLN6 NM_017882.2(CLN6): c.139C> T (p.Leu47Phe) single nucleotide variant Pathogenic rs154774635 GRCh37 Chromosome 15, 68510933: 68510933
6 CLN6 NM_017882.2(CLN6): c.139C> T (p.Leu47Phe) single nucleotide variant Pathogenic rs154774635 GRCh38 Chromosome 15, 68218595: 68218595
7 CLN6 NM_017882.2(CLN6): c.17G> C (p.Arg6Thr) single nucleotide variant Pathogenic rs154774636 GRCh37 Chromosome 15, 68521906: 68521906
8 CLN6 NM_017882.2(CLN6): c.17G> C (p.Arg6Thr) single nucleotide variant Pathogenic rs154774636 GRCh38 Chromosome 15, 68229568: 68229568
9 CLN6 NM_017882.2(CLN6): c.53C> T (p.Ala18Val) single nucleotide variant Conflicting interpretations of pathogenicity rs547125345 GRCh37 Chromosome 15, 68521870: 68521870
10 CLN6 NM_017882.2(CLN6): c.53C> T (p.Ala18Val) single nucleotide variant Conflicting interpretations of pathogenicity rs547125345 GRCh38 Chromosome 15, 68229532: 68229532
11 CLN6 NM_017882.2(CLN6): c.923G> C (p.Ser308Thr) single nucleotide variant Conflicting interpretations of pathogenicity rs143578698 GRCh37 Chromosome 15, 68500491: 68500491
12 CLN6 NM_017882.2(CLN6): c.923G> C (p.Ser308Thr) single nucleotide variant Conflicting interpretations of pathogenicity rs143578698 GRCh38 Chromosome 15, 68208153: 68208153

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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