SCAR21
MCID: SPN381
MIFTS: 35

Spinocerebellar Ataxia, Autosomal Recessive 21 (SCAR21)

Categories: Ear diseases, Eye diseases, Fetal diseases, Genetic diseases, Liver diseases, Mental diseases, Metabolic diseases, Muscle diseases, Neuronal diseases, Rare diseases, Skin diseases

Aliases & Classifications for Spinocerebellar Ataxia, Autosomal Recessive 21

MalaCards integrated aliases for Spinocerebellar Ataxia, Autosomal Recessive 21:

Name: Spinocerebellar Ataxia, Autosomal Recessive 21 56 29 6
Scar21 56 12 58 73
Acute Infantile Liver Failure-Cerebellar Ataxia-Peripheral Sensory Motor Neuropathy Syndrome 12 58
Spinocerebellar Ataxia, Autosomal Recessive 21, with Hepatopathy 56 73
Autosomal Recessive Spinocerebellar Ataxia 21 12 15
Cholestasis, Low Ggt, Acute Liver Failure, and Neurodegeneration Syndrome; Calfan 56
Cholestasis, Low Ggt, Acute Liver Failure, and Neurodegeneration Syndrome 56
Autosomal Recessive Spinocerebellar Ataxia 21 with Hepatopathy 12
Autosomal Recessive Spinocerebellar Ataxia Type 21 58
Spinocerebellar Ataxia, Autosomal Recessive, 21 73
Calfan Syndrome 6
Calfan 56

Characteristics:

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
highly variable phenotype
onset of episodic acute liver dysfunction in first 2 years of life
liver failure episodes associated with fever
liver failure episodes decrease or cease in later childhood
later onset of variable neurologic features


HPO:

31
spinocerebellar ataxia, autosomal recessive 21:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases
Rare hepatic diseases


Summaries for Spinocerebellar Ataxia, Autosomal Recessive 21

OMIM : 56 Autosomal recessive spinocerebellar ataxia-21 is a neurologic disorder characterized by onset of cerebellar ataxia associated with cerebellar atrophy in early childhood. Affected individuals also have recurrent episodes of liver failure in the first decade, resulting in chronic liver fibrosis, as well as later onset of a peripheral neuropathy. Mild learning disabilities may also occur (summary by Schmidt et al., 2015). The phenotype is highly variable: all patients appear to have episodic and severe liver dysfunction in early childhood that tends to resolve with age. Affected individuals also show mild developmental or language delay and/or later onset of variable neurologic features, such as motor dysfunction (summary by Lenz et al., 2018). (616719)

MalaCards based summary : Spinocerebellar Ataxia, Autosomal Recessive 21, also known as scar21, is related to spinocerebellar ataxia 21 and cholestasis. An important gene associated with Spinocerebellar Ataxia, Autosomal Recessive 21 is SCYL1 (SCY1 Like Pseudokinase 1). Affiliated tissues include liver, cerebellum and spinal cord, and related phenotypes are global developmental delay and intellectual disability, mild

Disease Ontology : 12 An autosomal recessive cerebellar ataxia that has material basis in homozygous or compound heterozygous mutation in the SCYL1 gene on chromosome 11q13.

UniProtKB/Swiss-Prot : 73 Spinocerebellar ataxia, autosomal recessive, 21: A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR21 is characterized by cerebellar atrophy and ataxia with onset in early childhood. Patients also manifest recurrent episodes of liver failure, hepatic fibrosis and a peripheral neuropathy.

Related Diseases for Spinocerebellar Ataxia, Autosomal Recessive 21

Diseases in the Spinocerebellar Ataxia 6 family:

Spinocerebellar Ataxia 31 Spinocerebellar Ataxia 29
Spinocerebellar Ataxia 34 Spinocerebellar Ataxia 1
Spinocerebellar Ataxia 7 Spinocerebellar Ataxia 2
Spinocerebellar Ataxia, Autosomal Recessive 2 Spinocerebellar Ataxia, Autosomal Recessive 3
Spinocerebellar Ataxia 4 Spinocerebellar Ataxia 5
Spinocerebellar Ataxia 10 Spinocerebellar Ataxia 12
Spinocerebellar Ataxia 11 Spinocerebellar Ataxia 13
Spinocerebellar Ataxia 14 Spinocerebellar Ataxia 15
Spinocerebellar Ataxia 17 Spinocerebellar Ataxia, Autosomal Recessive 4
Spinocerebellar Ataxia 19 Spinocerebellar Ataxia 21
Spinocerebellar Ataxia 18 Spinocerebellar Ataxia, Autosomal Recessive 6
Spinocerebellar Ataxia 20 Spinocerebellar Ataxia 25
Spinocerebellar Ataxia 8 Spinocerebellar Ataxia, Autosomal Recessive 7
Spinocerebellar Ataxia 26 Spinocerebellar Ataxia 27
Spinocerebellar Ataxia 23 Spinocerebellar Ataxia 28
Spinocerebellar Ataxia, Autosomal Recessive 8 Spinocerebellar Ataxia 9
Spinocerebellar Ataxia 30 Spinocerebellar Ataxia, Autosomal Recessive 10
Spinocerebellar Ataxia 35 Spinocerebellar Ataxia 32
Spinocerebellar Ataxia 36 Spinocerebellar Ataxia, Autosomal Recessive 11
Spinocerebellar Ataxia, Autosomal Recessive 12 Spinocerebellar Ataxia, Autosomal Recessive 13
Spinocerebellar Ataxia, Autosomal Recessive 14 Spinocerebellar Ataxia, Autosomal Recessive 15
Spinocerebellar Ataxia, Autosomal Recessive 16 Spinocerebellar Ataxia 37
Spinocerebellar Ataxia 38 Spinocerebellar Ataxia 40
Spinocerebellar Ataxia, Autosomal Recessive 17 Spinocerebellar Ataxia, Autosomal Recessive 18
Spinocerebellar Ataxia, Autosomal Recessive 20 Spinocerebellar Ataxia 41
Spinocerebellar Ataxia, Autosomal Recessive 21 Spinocerebellar Ataxia 42
Spinocerebellar Ataxia, Autosomal Recessive 22 Spinocerebellar Ataxia, Autosomal Recessive 23
Spinocerebellar Ataxia 43 Spinocerebellar Ataxia, Autosomal Recessive 24
Spinocerebellar Ataxia, Autosomal Recessive 25 Spinocerebellar Ataxia, Autosomal Recessive 26
Spinocerebellar Ataxia 44 Spinocerebellar Ataxia 45
Spinocerebellar Ataxia 46 Spinocerebellar Ataxia 47
Spinocerebellar Ataxia 48 Spinocerebellar Ataxia, Autosomal Recessive 27
Spinocerebellar Ataxia Type 19/22 Grid2-Related Spinocerebellar Ataxia
Spinocerebellar Ataxia Autosomal Recessive 5

Diseases related to Spinocerebellar Ataxia, Autosomal Recessive 21 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 12)
# Related Disease Score Top Affiliating Genes
1 spinocerebellar ataxia 21 30.0 TMEM240 SCYL1
2 cholestasis 10.3
3 acute liver failure 10.3
4 ataxia and polyneuropathy, adult-onset 10.2
5 respiratory failure 10.2
6 peripheral nervous system disease 10.2
7 neuropathy 10.2
8 spastic paraplegia 46, autosomal recessive 9.7 KIF1C GBA2
9 spastic ataxia 9.5 KIF1C GBA2
10 autosomal recessive cerebellar ataxia 9.5 UBA5 GBA2
11 spastic paraplegia 73, autosomal dominant 8.7 UBA5 KIF1C GBA2 FAT2
12 spastic paraplegia 76, autosomal recessive 8.7 UBA5 KIF1C GBA2 FAT2

Graphical network of the top 20 diseases related to Spinocerebellar Ataxia, Autosomal Recessive 21:



Diseases related to Spinocerebellar Ataxia, Autosomal Recessive 21

Symptoms & Phenotypes for Spinocerebellar Ataxia, Autosomal Recessive 21

Human phenotypes related to Spinocerebellar Ataxia, Autosomal Recessive 21:

58 31 (show all 33)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 global developmental delay 58 31 frequent (33%) Frequent (79-30%) HP:0001263
2 intellectual disability, mild 58 31 occasional (7.5%) Frequent (79-30%) HP:0001256
3 fever 58 31 frequent (33%) Frequent (79-30%) HP:0001945
4 hepatic fibrosis 58 31 frequent (33%) Frequent (79-30%) HP:0001395
5 gait ataxia 58 31 frequent (33%) Frequent (79-30%) HP:0002066
6 intention tremor 58 31 frequent (33%) Frequent (79-30%) HP:0002080
7 paresthesia 58 31 frequent (33%) Frequent (79-30%) HP:0003401
8 hyporeflexia 58 31 frequent (33%) Frequent (79-30%) HP:0001265
9 acute hepatic failure 58 31 frequent (33%) Frequent (79-30%) HP:0006554
10 progressive cerebellar ataxia 58 31 frequent (33%) Frequent (79-30%) HP:0002073
11 saccadic smooth pursuit 58 31 frequent (33%) Frequent (79-30%) HP:0001152
12 cerebellar vermis atrophy 58 31 frequent (33%) Frequent (79-30%) HP:0006855
13 generalized limb muscle atrophy 58 31 frequent (33%) Frequent (79-30%) HP:0009055
14 distal lower limb muscle weakness 58 31 frequent (33%) Frequent (79-30%) HP:0009053
15 frequent falls 58 31 frequent (33%) Frequent (79-30%) HP:0002359
16 hepatosplenomegaly 58 31 frequent (33%) Frequent (79-30%) HP:0001433
17 sensory impairment 58 31 frequent (33%) Frequent (79-30%) HP:0003474
18 dysmetric saccades 58 31 frequent (33%) Frequent (79-30%) HP:0000641
19 stuttering 58 31 frequent (33%) Frequent (79-30%) HP:0025268
20 spasticity 58 31 occasional (7.5%) Very rare (<4-1%) HP:0001257
21 hyperreflexia 58 31 occasional (7.5%) Very rare (<4-1%) HP:0001347
22 talipes equinovarus 58 31 occasional (7.5%) Very rare (<4-1%) HP:0001762
23 optic atrophy 58 31 very rare (1%) Very rare (<4-1%) HP:0000648
24 tremor 31 HP:0001337
25 splenomegaly 31 HP:0001744
26 hepatomegaly 31 HP:0002240
27 peripheral neuropathy 58 Frequent (79-30%)
28 reduced visual acuity 58 Excluded (0%)
29 motor delay 31 HP:0001270
30 hepatic failure 31 HP:0001399
31 cerebellar atrophy 31 HP:0001272
32 sensorimotor neuropathy 31 HP:0007141
33 distal sensory impairment 31 HP:0002936

Symptoms via clinical synopsis from OMIM:

56
Skeletal Spine:
scoliosis
lordosis

Abdomen Spleen:
splenomegaly

Skeletal Pelvis:
hip dysplasia

Neurologic Peripheral Nervous System:
hyporeflexia
sensorimotor neuropathy
distal sensory impairment
axonal neuropathy

Growth Height:
short stature (in some patients)

Skeletal Feet:
pes equinovarus (1 patient)

Chest Ribs Sternum Clavicles And Scapulae:
rib anomalies (in some patients)

Laboratory Abnormalities:
elevated liver enzymes during acute episodes
liver enzymes tend to normalize after acute episode
lesser elevation of ggt

Neurologic Central Nervous System:
tremor
dysmetria
frequent falls
steppage gait
language impairment
more
Abdomen Liver:
hepatomegaly
hepatic fibrosis
cholestasis
microvesicular steatosis
bridging fibrosis
more
Skin Nails Hair Skin:
jaundice
icterus

Head And Neck Eyes:
oculomotor apraxia
upward gaze palsy
saccadic pursuit
cerebellar oculomotor disturbance
subclinical optic atrophy (1 family)
more
Muscle Soft Tissue:
axial hypotonia
muscle atrophy, upper and lower limbs
muscle weakness, distal, lower limbs, due to peripheral neuropathy

Head And Neck Head:
microcephaly, mild (in some patients)

Skeletal:
skeletal anomalies (in some patients)

Clinical features from OMIM:

616719

Drugs & Therapeutics for Spinocerebellar Ataxia, Autosomal Recessive 21

Search Clinical Trials , NIH Clinical Center for Spinocerebellar Ataxia, Autosomal Recessive 21

Genetic Tests for Spinocerebellar Ataxia, Autosomal Recessive 21

Genetic tests related to Spinocerebellar Ataxia, Autosomal Recessive 21:

# Genetic test Affiliating Genes
1 Spinocerebellar Ataxia, Autosomal Recessive 21 29 SCYL1

Anatomical Context for Spinocerebellar Ataxia, Autosomal Recessive 21

MalaCards organs/tissues related to Spinocerebellar Ataxia, Autosomal Recessive 21:

40
Liver, Cerebellum, Spinal Cord, Eye, Skin

Publications for Spinocerebellar Ataxia, Autosomal Recessive 21

Articles related to Spinocerebellar Ataxia, Autosomal Recessive 21:

# Title Authors PMID Year
1
SCYL1 variants cause a syndrome with low γ-glutamyl-transferase cholestasis, acute liver failure, and neurodegeneration (CALFAN). 56 6
29419818 2018
2
On CALFAN syndrome: report of a patient with a novel variant in SCYL1 gene and recurrent respiratory failure. 56
30531813 2019
3
Disruptive SCYL1 Mutations Underlie a Syndrome Characterized by Recurrent Episodes of Liver Failure, Peripheral Neuropathy, Cerebellar Atrophy, and Ataxia. 56
26581903 2015
4
An early onset progressive motor neuron disorder in Scyl1-deficient mice is associated with mislocalization of TDP-43. 56
23175812 2012
5
Mutation in the Scyl1 gene encoding amino-terminal kinase-like protein causes a recessive form of spinocerebellar neurodegeneration. 56
17571074 2007
6
Variant in SCYL1 gene causes aberrant splicing in a family with cerebellar ataxia, recurrent episodes of liver failure, and growth retardation. 61
30258122 2019
7
Hereditary ataxias and paraparesias: clinical and genetic update. 61
29847346 2018
8
Spinocerebellar Ataxia-21 in a Turkish Child. 61
29720801 2018

Variations for Spinocerebellar Ataxia, Autosomal Recessive 21

ClinVar genetic disease variations for Spinocerebellar Ataxia, Autosomal Recessive 21:

6 ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 SCYL1 NM_020680.4(SCYL1):c.169C>T (p.Gln57Ter)SNV Pathogenic 446293 rs1554967681 11:65293102-65293102 11:65525631-65525631
2 SCYL1 NM_020680.4(SCYL1):c.256G>T (p.Glu86Ter)SNV Pathogenic 446292 rs1554967761 11:65293395-65293395 11:65525924-65525924
3 SCYL1 NM_020680.4(SCYL1):c.314C>T (p.Ala105Val)SNV Pathogenic 446294 rs942522644 11:65293453-65293453 11:65525982-65525982
4 SCYL1 NM_020680.4(SCYL1):c.1433A>G (p.Asp478Gly)SNV Pathogenic 446291 rs1554969925 11:65303470-65303470 11:65535999-65535999
5 SCYL1 NM_020680.4(SCYL1):c.1882C>T (p.Gln628Ter)SNV Pathogenic 446290 rs1554970375 11:65304522-65304522 11:65537051-65537051
6 SCYL1 NM_020680.4(SCYL1):c.526A>T (p.Lys176Ter)SNV Pathogenic 692036 11:65293745-65293745 11:65526274-65526274
7 SCYL1 NM_020680.4(SCYL1):c.1412C>T (p.Ala471Val)SNV Likely pathogenic 548462 rs1554969894 11:65303449-65303449 11:65535978-65535978
8 SCYL1 NM_020680.4(SCYL1):c.1507T>C (p.Cys503Arg)SNV Uncertain significance 801001 11:65303544-65303544 11:65536073-65536073

Expression for Spinocerebellar Ataxia, Autosomal Recessive 21

Search GEO for disease gene expression data for Spinocerebellar Ataxia, Autosomal Recessive 21.

Pathways for Spinocerebellar Ataxia, Autosomal Recessive 21

GO Terms for Spinocerebellar Ataxia, Autosomal Recessive 21

Cellular components related to Spinocerebellar Ataxia, Autosomal Recessive 21 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 Golgi apparatus GO:0005794 9.02 UBA5 SCYL1 KIF1C GBA2 FAT2

Biological processes related to Spinocerebellar Ataxia, Autosomal Recessive 21 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 retrograde vesicle-mediated transport, Golgi to ER GO:0006890 8.62 KIF1C SCYL1

Sources for Spinocerebellar Ataxia, Autosomal Recessive 21

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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