SPAHGC
MCID: SPS211
MIFTS: 27

Spasticity, Childhood-Onset, with Hyperglycinemia (SPAHGC)

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

Aliases & Classifications for Spasticity, Childhood-Onset, with Hyperglycinemia

MalaCards integrated aliases for Spasticity, Childhood-Onset, with Hyperglycinemia:

Name: Spasticity, Childhood-Onset, with Hyperglycinemia 58 76 30 6
Spahgc 58 76
Childhood-Onset Spasticity with Variant Non-Ketotic Hyperglycinemia 60
Childhood-Onset Spasticity with Hyperglycinemia 60
Spasticity-Ataxia-Gait Anomalies Syndrome 60

Characteristics:

Orphanet epidemiological data:

60
childhood-onset spasticity with hyperglycinemia
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood;

OMIM:

58
Inheritance:
autosomal recessive

Miscellaneous:
three unrelated patients have been reported (last curated march 2016)
onset in first decade after normal early development
slowly progressive or static


HPO:

33
spasticity, childhood-onset, with hyperglycinemia:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Spasticity, Childhood-Onset, with Hyperglycinemia

OMIM : 58 Childhood-onset spasticity with hyperglycinemia is an autosomal recessive disorder characterized by onset of slowly progressive spasticity that results in impaired gait in the first decade of life. Imaging of the central nervous system shows leukodystrophy and/or lesions in the upper spinal cord. More variable features include visual defects and mild learning disabilities. Serum glycine is increased, but CSF glycine is only mildly increased or normal; serum lactate is normal. The disorder represents a form of 'variant' nonketotic hyperglycinemia and is distinct from classic nonketotic hyperglycinemia (NKH, or GCE; 605899), which is characterized by significantly increased CSF glycine. Several forms of 'variant' NKH, including SPAHGC, appear to result from defects of mitochondrial lipoate biosynthesis (summary by Baker et al., 2014). (616859)

MalaCards based summary : Spasticity, Childhood-Onset, with Hyperglycinemia, is also known as spahgc. An important gene associated with Spasticity, Childhood-Onset, with Hyperglycinemia is GLRX5 (Glutaredoxin 5). Affiliated tissues include spinal cord and eye, and related phenotypes are progressive spasticity and nonketotic hyperglycinemia

UniProtKB/Swiss-Prot : 76 Spasticity, childhood-onset, with hyperglycinemia: An autosomal recessive disorder characterized by childhood-onset of spasticity, spinal lesions, leukodystrophy, optic atrophy in some patients, non-ketotic hyperglycinemia, and defective enzymatic glycine cleavage. Glycine levels in the cerebrospinal fluid are mildly increased in some but not all patients. The increase is less pronounced than in patients with classic non-ketotic hyperglycinemia.

Related Diseases for Spasticity, Childhood-Onset, with Hyperglycinemia

Symptoms & Phenotypes for Spasticity, Childhood-Onset, with Hyperglycinemia

Human phenotypes related to Spasticity, Childhood-Onset, with Hyperglycinemia:

60 33 (show all 32)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 progressive spasticity 60 33 hallmark (90%) Very frequent (99-80%) HP:0002191
2 nonketotic hyperglycinemia 60 33 hallmark (90%) Very frequent (99-80%) HP:0008288
3 nystagmus 60 33 frequent (33%) Frequent (79-30%) HP:0000639
4 hyperreflexia 60 33 frequent (33%) Frequent (79-30%) HP:0001347
5 visual impairment 60 33 frequent (33%) Frequent (79-30%) HP:0000505
6 optic atrophy 60 33 frequent (33%) Frequent (79-30%) HP:0000648
7 babinski sign 60 33 frequent (33%) Frequent (79-30%) HP:0003487
8 spinal cord lesion 60 33 frequent (33%) Frequent (79-30%) HP:0100561
9 leukodystrophy 60 33 frequent (33%) Frequent (79-30%) HP:0002415
10 spastic diplegia 60 33 frequent (33%) Frequent (79-30%) HP:0001264
11 unsteady gait 60 33 frequent (33%) Frequent (79-30%) HP:0002317
12 spastic dysarthria 60 33 frequent (33%) Frequent (79-30%) HP:0002464
13 decreased activity of the pyruvate dehydrogenase complex 60 33 frequent (33%) Frequent (79-30%) HP:0002928
14 short attention span 60 33 frequent (33%) Frequent (79-30%) HP:0000736
15 loss of ability to walk in early childhood 60 33 frequent (33%) Frequent (79-30%) HP:0008945
16 ataxia 60 33 occasional (7.5%) Occasional (29-5%) HP:0001251
17 developmental regression 60 33 occasional (7.5%) Occasional (29-5%) HP:0002376
18 irritability 60 33 occasional (7.5%) Occasional (29-5%) HP:0000737
19 feeding difficulties 60 33 occasional (7.5%) Occasional (29-5%) HP:0011968
20 myoclonus 60 33 occasional (7.5%) Occasional (29-5%) HP:0001336
21 generalized hypotonia 60 33 occasional (7.5%) Occasional (29-5%) HP:0001290
22 left ventricular hypertrophy 60 33 very rare (1%) Very rare (<4-1%) HP:0001712
23 seizures 33 HP:0001250
24 dysarthria 33 HP:0001260
25 gait disturbance 33 HP:0001288
26 hypertonia 60 Frequent (79-30%)
27 cognitive impairment 60 Excluded (0%)
28 strabismus 33 HP:0000486
29 increased serum lactate 60 Excluded (0%)
30 hypoplasia of the corpus callosum 33 HP:0002079
31 spastic ataxia 33 HP:0002497
32 hyperglycinemia 33 HP:0002154

Symptoms via clinical synopsis from OMIM:

58
Neurologic Central Nervous System:
spasticity
dysarthria
hyperreflexia
leukodystrophy
pyramidal signs
more
Head And Neck Eyes:
nystagmus (patient a)
optic atrophy (patient a)
visual impairment (patient a)

Laboratory Abnormalities:
decreased activity of the pyruvate dehydrogenase complex (pdh)
increased serum glycine
mildly increased csf glycine (in some patients)
deficient glycine cleavage enzyme activity
normal serum lactate

Clinical features from OMIM:

616859

Drugs & Therapeutics for Spasticity, Childhood-Onset, with Hyperglycinemia

Search Clinical Trials , NIH Clinical Center for Spasticity, Childhood-Onset, with Hyperglycinemia

Genetic Tests for Spasticity, Childhood-Onset, with Hyperglycinemia

Genetic tests related to Spasticity, Childhood-Onset, with Hyperglycinemia:

# Genetic test Affiliating Genes
1 Spasticity, Childhood-Onset, with Hyperglycinemia 30 GLRX5

Anatomical Context for Spasticity, Childhood-Onset, with Hyperglycinemia

MalaCards organs/tissues related to Spasticity, Childhood-Onset, with Hyperglycinemia:

42
Spinal Cord, Eye

Publications for Spasticity, Childhood-Onset, with Hyperglycinemia

Articles related to Spasticity, Childhood-Onset, with Hyperglycinemia:

# Title Authors Year
1
Functional Analysis of GLRX5 Mutants Reveals Distinct Functionalities of GLRX5 Protein. ( 26100117 )
2016
2
Variant non ketotic hyperglycinemia is caused by mutations in LIAS, BOLA3 and the novel gene GLRX5. ( 24334290 )
2014

Variations for Spasticity, Childhood-Onset, with Hyperglycinemia

ClinVar genetic disease variations for Spasticity, Childhood-Onset, with Hyperglycinemia:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 GLRX5 NM_016417.2(GLRX5): c.151_153delAAG (p.Lys51del) deletion Pathogenic rs869320757 GRCh37 Chromosome 14, 96001577: 96001579
2 GLRX5 NM_016417.2(GLRX5): c.151_153delAAG (p.Lys51del) deletion Pathogenic rs869320757 GRCh38 Chromosome 14, 95535240: 95535242
3 GLRX5 NM_016417.2(GLRX5): c.86_93dupTGCGGGCG (p.Ala32Cysfs) duplication Pathogenic rs869320758 GRCh38 Chromosome 14, 95535175: 95535182
4 GLRX5 NM_016417.2(GLRX5): c.86_93dupTGCGGGCG (p.Ala32Cysfs) duplication Pathogenic rs869320758 GRCh37 Chromosome 14, 96001512: 96001519

Expression for Spasticity, Childhood-Onset, with Hyperglycinemia

Search GEO for disease gene expression data for Spasticity, Childhood-Onset, with Hyperglycinemia.

Pathways for Spasticity, Childhood-Onset, with Hyperglycinemia

GO Terms for Spasticity, Childhood-Onset, with Hyperglycinemia

Cellular components related to Spasticity, Childhood-Onset, with Hyperglycinemia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 nucleolus GO:0005730 8.96 SCARNA13 SNHG10
2 Cajal body GO:0015030 8.62 SCARNA13 SNHG10

Biological processes related to Spasticity, Childhood-Onset, with Hyperglycinemia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 RNA processing GO:0006396 8.62 SCARNA13 SNHG10

Sources for Spasticity, Childhood-Onset, with Hyperglycinemia

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
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