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 57 75 29 6
Spahgc 57 75
Childhood-Onset Spasticity with Variant Non-Ketotic Hyperglycinemia 59
Childhood-Onset Spasticity with Hyperglycinemia 59
Spasticity-Ataxia-Gait Anomalies Syndrome 59

Characteristics:

Orphanet epidemiological data:

59
childhood-onset spasticity with hyperglycinemia
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood;

OMIM:

57
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:

32
spasticity, childhood-onset, with hyperglycinemia:
Inheritance autosomal recessive inheritance


Classifications:



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)

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 nystagmus and ataxia

UniProtKB/Swiss-Prot : 75 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

Symptoms via clinical synopsis from OMIM:

57
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

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

59 32 (show all 32)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 nystagmus 59 32 frequent (33%) Frequent (79-30%) HP:0000639
2 ataxia 59 32 occasional (7.5%) Occasional (29-5%) HP:0001251
3 hyperreflexia 59 32 frequent (33%) Frequent (79-30%) HP:0001347
4 developmental regression 59 32 occasional (7.5%) Occasional (29-5%) HP:0002376
5 visual impairment 59 32 frequent (33%) Frequent (79-30%) HP:0000505
6 optic atrophy 59 32 frequent (33%) Frequent (79-30%) HP:0000648
7 irritability 59 32 occasional (7.5%) Occasional (29-5%) HP:0000737
8 feeding difficulties 59 32 occasional (7.5%) Occasional (29-5%) HP:0011968
9 myoclonus 59 32 occasional (7.5%) Occasional (29-5%) HP:0001336
10 babinski sign 59 32 frequent (33%) Frequent (79-30%) HP:0003487
11 left ventricular hypertrophy 59 32 very rare (1%) Very rare (<4-1%) HP:0001712
12 progressive spasticity 59 32 hallmark (90%) Very frequent (99-80%) HP:0002191
13 generalized hypotonia 59 32 occasional (7.5%) Occasional (29-5%) HP:0001290
14 spinal cord lesion 59 32 frequent (33%) Frequent (79-30%) HP:0100561
15 leukodystrophy 59 32 frequent (33%) Frequent (79-30%) HP:0002415
16 spastic diplegia 59 32 frequent (33%) Frequent (79-30%) HP:0001264
17 unsteady gait 59 32 frequent (33%) Frequent (79-30%) HP:0002317
18 nonketotic hyperglycinemia 59 32 hallmark (90%) Very frequent (99-80%) HP:0008288
19 spastic dysarthria 59 32 frequent (33%) Frequent (79-30%) HP:0002464
20 decreased activity of the pyruvate dehydrogenase complex 59 32 frequent (33%) Frequent (79-30%) HP:0002928
21 short attention span 59 32 frequent (33%) Frequent (79-30%) HP:0000736
22 loss of ability to walk in early childhood 59 32 frequent (33%) Frequent (79-30%) HP:0008945
23 seizures 32 HP:0001250
24 dysarthria 32 HP:0001260
25 gait disturbance 32 HP:0001288
26 hypertonia 59 Frequent (79-30%)
27 cognitive impairment 59 Excluded (0%)
28 strabismus 32 HP:0000486
29 increased serum lactate 59 Excluded (0%)
30 hypoplasia of the corpus callosum 32 HP:0002079
31 spastic ataxia 32 HP:0002497
32 hyperglycinemia 32 HP:0002154

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:

41
Spinal Cord, Eye

Publications for Spasticity, Childhood-Onset, with Hyperglycinemia

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 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
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45 MESH via Orphanet
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49 NCI
50 NCIt
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57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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