SPAHGC
MCID: SPS211
MIFTS: 24

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 57 72 29 6
Spahgc 57 72
Childhood-Onset Spasticity with Variant Non-Ketotic Hyperglycinemia 58
Childhood-Onset Spasticity with Hyperglycinemia 58
Spasticity-Ataxia-Gait Anomalies Syndrome 58

Characteristics:

Orphanet epidemiological data:

58
childhood-onset spasticity with hyperglycinemia
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood;

OMIM®:

57 (Updated 20-May-2021)
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:

31
spasticity, childhood-onset, with hyperglycinemia:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases
Inborn errors of metabolism


Summaries for Spasticity, Childhood-Onset, with Hyperglycinemia

OMIM® : 57 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) (Updated 20-May-2021)

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 : 72 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:

58 31 (show all 32)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 progressive spasticity 58 31 hallmark (90%) Very frequent (99-80%) HP:0002191
2 nonketotic hyperglycinemia 58 31 hallmark (90%) Very frequent (99-80%) HP:0008288
3 hyperreflexia 58 31 frequent (33%) Frequent (79-30%) HP:0001347
4 nystagmus 58 31 frequent (33%) Frequent (79-30%) HP:0000639
5 visual impairment 58 31 frequent (33%) Frequent (79-30%) HP:0000505
6 optic atrophy 58 31 frequent (33%) Frequent (79-30%) HP:0000648
7 babinski sign 58 31 frequent (33%) Frequent (79-30%) HP:0003487
8 leukodystrophy 58 31 frequent (33%) Frequent (79-30%) HP:0002415
9 spastic diplegia 58 31 frequent (33%) Frequent (79-30%) HP:0001264
10 unsteady gait 58 31 frequent (33%) Frequent (79-30%) HP:0002317
11 short attention span 58 31 frequent (33%) Frequent (79-30%) HP:0000736
12 spinal cord lesion 58 31 frequent (33%) Frequent (79-30%) HP:0100561
13 spastic dysarthria 58 31 frequent (33%) Frequent (79-30%) HP:0002464
14 decreased activity of the pyruvate dehydrogenase complex 58 31 frequent (33%) Frequent (79-30%) HP:0002928
15 loss of ability to walk in early childhood 58 31 frequent (33%) Frequent (79-30%) HP:0008945
16 ataxia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001251
17 developmental regression 58 31 occasional (7.5%) Occasional (29-5%) HP:0002376
18 myoclonus 58 31 occasional (7.5%) Occasional (29-5%) HP:0001336
19 irritability 58 31 occasional (7.5%) Occasional (29-5%) HP:0000737
20 feeding difficulties 58 31 occasional (7.5%) Occasional (29-5%) HP:0011968
21 generalized hypotonia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001290
22 left ventricular hypertrophy 58 31 very rare (1%) Very rare (<4-1%) HP:0001712
23 dysarthria 31 HP:0001260
24 gait disturbance 31 HP:0001288
25 hypertonia 58 Frequent (79-30%)
26 cognitive impairment 58 Excluded (0%)
27 strabismus 31 HP:0000486
28 increased serum lactate 58 Excluded (0%)
29 hypoplasia of the corpus callosum 31 HP:0002079
30 spastic ataxia 31 HP:0002497
31 hyperglycinemia 31 HP:0002154
32 seizure 31 HP:0001250

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Neurologic Central Nervous System:
spasticity
hyperreflexia
dysarthria
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 (Updated 20-May-2021)

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 29 GLRX5

Anatomical Context for Spasticity, Childhood-Onset, with Hyperglycinemia

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

40
Spinal Cord, Eye

Publications for Spasticity, Childhood-Onset, with Hyperglycinemia

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

# Title Authors PMID Year
1
Functional Analysis of GLRX5 Mutants Reveals Distinct Functionalities of GLRX5 Protein. 6 57
26100117 2016
2
Variant non ketotic hyperglycinemia is caused by mutations in LIAS, BOLA3 and the novel gene GLRX5. 6 57
24334290 2014
3
Unusual spinal cord lesions in late-onset non-ketotic hyperglycinemia. 57
21471552 2011

Variations for Spasticity, Childhood-Onset, with Hyperglycinemia

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

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 GLRX5 NM_016417.3(GLRX5):c.148_150AAG[1] (p.Lys51del) Microsatellite Pathogenic 224512 rs869320757 GRCh37: 14:96001573-96001575
GRCh38: 14:95535236-95535238
2 GLRX5 NM_016417.3(GLRX5):c.86_93dup (p.Ala32fs) Duplication Pathogenic 224513 rs869320758 GRCh37: 14:96001505-96001506
GRCh38: 14:95535168-95535169

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

Sources for Spasticity, Childhood-Onset, with Hyperglycinemia

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 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
Content
Loading form....