SMAJI
MCID: SPN447
MIFTS: 22

Spinal Muscular Atrophy, Infantile, James Type (SMAJI)

Categories: Genetic diseases, Muscle diseases, Neuronal diseases, Respiratory diseases

Aliases & Classifications for Spinal Muscular Atrophy, Infantile, James Type

MalaCards integrated aliases for Spinal Muscular Atrophy, Infantile, James Type:

Name: Spinal Muscular Atrophy, Infantile, James Type 57 72 6
Smaji 57 72

Characteristics:

OMIM®:

57 (Updated 05-Apr-2021)
Miscellaneous:
motor regression
progressive disorder
lower limbs more affected than upper limbs
onset in infancy (range birth to first months of life)
normal early development prior to onset of symptoms (in some patients)

Inheritance:
autosomal dominant


HPO:

31
spinal muscular atrophy, infantile, james type:
Inheritance autosomal dominant inheritance
Onset and clinical course infantile onset


Classifications:



Summaries for Spinal Muscular Atrophy, Infantile, James Type

OMIM® : 57 The James type of infantile spinal muscular atrophy (SMAJI) is a severe neuromuscular disorder with onset of hypotonia in the first weeks or months of life. Some patients may have normal early motor development prior to the onset of symptoms, but all show delayed motor milestones with loss of previous motor skills in the first year of life. There is muscle weakness and atrophy, primarily affecting distal muscles, resulting in the inability to walk independently and causing impairment of fine motor skills of the hands. The disorder is slowly progressive: additional features may include feeding difficulties with failure to thrive, foot deformities, hyperlordosis, scoliosis, vocal cord weakness, and respiratory insufficiency, which may require intervention. Laboratory studies are most consistent with a motor neuronopathy, although skeletal muscle biopsy may also show myopathic features. This disorder is considered to be at the most severe end of the phenotypic spectrum of disorders caused by mutations in the GARS1 gene. The disorder is phenotypically similar to SMA1 (253300) (summary by Eskuri et al., 2012; Markovitz et al., 2020). (619042) (Updated 05-Apr-2021)

MalaCards based summary : Spinal Muscular Atrophy, Infantile, James Type, is also known as smaji. An important gene associated with Spinal Muscular Atrophy, Infantile, James Type is GARS1 (Glycyl-TRNA Synthetase 1). Affiliated tissues include skeletal muscle, spinal cord and eye, and related phenotypes are scoliosis and respiratory insufficiency

UniProtKB/Swiss-Prot : 72 Spinal muscular atrophy, infantile, James type: An autosomal dominant form of spinal muscular atrophy, a group of neuromuscular disorders characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. SMAJI is a severe disease characterized by hypotonia manifesting in the first weeks or months of life, delayed motor development, motor regression, and muscle weakness and atrophy primarily affecting distal muscles. Additional variable features include feeding difficulties, poor overall growth, foot deformities, kyphosis, hyperlordosis, scoliosis, vocal cord dysfunction, and respiratory insufficiency.

Related Diseases for Spinal Muscular Atrophy, Infantile, James Type

Symptoms & Phenotypes for Spinal Muscular Atrophy, Infantile, James Type

Human phenotypes related to Spinal Muscular Atrophy, Infantile, James Type:

31 (show all 15)
# Description HPO Frequency HPO Source Accession
1 scoliosis 31 very rare (1%) HP:0002650
2 respiratory insufficiency 31 very rare (1%) HP:0002093
3 short stature 31 very rare (1%) HP:0004322
4 type 1 muscle fiber predominance 31 very rare (1%) HP:0003803
5 areflexia 31 very rare (1%) HP:0001284
6 weak voice 31 very rare (1%) HP:0001621
7 hip contracture 31 very rare (1%) HP:0003273
8 generalized hypotonia 31 very rare (1%) HP:0001290
9 distal muscle weakness 31 very rare (1%) HP:0002460
10 increased variability in muscle fiber diameter 31 very rare (1%) HP:0003557
11 distal amyotrophy 31 very rare (1%) HP:0003693
12 lumbar hyperlordosis 31 very rare (1%) HP:0002938
13 lower limb muscle weakness 31 very rare (1%) HP:0007340
14 muscle fibrillation 31 very rare (1%) HP:0010546
15 delayed ability to walk 31 very rare (1%) HP:0031936

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Growth Other:
failure to thrive
poor overall growth

Respiratory:
respiratory insufficiency
stridor
decreased forced vital capacity
tracheostomy
mechanical ventilation
more
Abdomen Gastrointestinal:
feeding difficulties
tube feeding

Skeletal Feet:
foot deformities

Muscle Soft Tissue:
facial muscle weakness, mild
denervation atrophy
fiber type variation seen on skeletal muscle biopsy
muscle weakness, neurogenic, distal more than proximal
muscle atrophy, neurogenic, distal more than proximal
more
Skeletal Hands:
claw hands

Voice:
decreased voice volume due to muscle weakness

Skeletal Spine:
scoliosis
kyphosis
hyperlordosis

Neurologic Peripheral Nervous System:
areflexia
hyporeflexia
axonal sensorimotor peripheral neuropathy
decreased cmap
sensory impairment (in some patients, but less pronounced than motor impairment)

Neurologic Central Nervous System:
motor regression
delayed motor development
no independent ambulation

Head And Neck Face:
facial muscle weakness, mild

Skeletal Pelvis:
hip contractures

Head And Neck Eyes:
external eye muscle weakness, mild

Clinical features from OMIM®:

619042 (Updated 05-Apr-2021)

Drugs & Therapeutics for Spinal Muscular Atrophy, Infantile, James Type

Search Clinical Trials , NIH Clinical Center for Spinal Muscular Atrophy, Infantile, James Type

Genetic Tests for Spinal Muscular Atrophy, Infantile, James Type

Anatomical Context for Spinal Muscular Atrophy, Infantile, James Type

MalaCards organs/tissues related to Spinal Muscular Atrophy, Infantile, James Type:

40
Skeletal Muscle, Spinal Cord, Eye

Publications for Spinal Muscular Atrophy, Infantile, James Type

Articles related to Spinal Muscular Atrophy, Infantile, James Type:

# Title Authors PMID Year
1
GARS-related disease in infantile spinal muscular atrophy: Implications for diagnosis and treatment. 57 6
32181591 2020
2
Clinical and Genetic Features in a Series of Eight Unrelated Patients with Neuropathy Due to Glycyl-tRNA Synthetase (GARS) Variants. 6 57
31985473 2020
3
Infantile onset CMT2D/dSMA V in monozygotic twins due to a mutation in the anticodon-binding domain of GARS. 57 6
22462675 2012
4
Severe childhood SMA and axonal CMT due to anticodon binding domain mutations in the GARS gene. 6 57
17101916 2006
5
Impaired function is a common feature of neuropathy-associated glycyl-tRNA synthetase mutations. 6
25168514 2014

Variations for Spinal Muscular Atrophy, Infantile, James Type

ClinVar genetic disease variations for Spinal Muscular Atrophy, Infantile, James Type:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 GARS1 NM_002047.4(GARS1):c.373G>A (p.Glu125Lys) SNV Pathogenic 208650 rs797044855 GRCh37: 7:30639611-30639611
GRCh38: 7:30599995-30599995
2 GARS1 NM_002047.4(GARS1):c.1955G>C (p.Gly652Ala) SNV Pathogenic 637543 rs747080824 GRCh37: 7:30671914-30671914
GRCh38: 7:30632298-30632298
3 GARS1 NM_002047.4(GARS1):c.1954G>C (p.Gly652Arg) SNV Pathogenic 981500 GRCh37: 7:30671913-30671913
GRCh38: 7:30632297-30632297
4 GARS1 NM_002047.4(GARS1):c.1001T>A (p.Ile334Asn) SNV Pathogenic 543227 rs1554338262 GRCh37: 7:30651831-30651831
GRCh38: 7:30612215-30612215

Expression for Spinal Muscular Atrophy, Infantile, James Type

Search GEO for disease gene expression data for Spinal Muscular Atrophy, Infantile, James Type.

Pathways for Spinal Muscular Atrophy, Infantile, James Type

GO Terms for Spinal Muscular Atrophy, Infantile, James Type

Sources for Spinal Muscular Atrophy, Infantile, James Type

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
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
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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