MCID: SPS211
MIFTS: 23

Spasticity, Childhood-Onset, with Hyperglycinemia

Categories: Genetic diseases, Neuronal diseases, Metabolic 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 related phenotypes are progressive spasticity and nonketotic hyperglycinemia

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

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

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 GRCh38 Chromosome 14, 95535240: 95535242
2 GLRX5 NM_016417.2(GLRX5): c.151_153delAAG (p.Lys51del) deletion Pathogenic rs869320757 GRCh37 Chromosome 14, 96001577: 96001579
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

Sources for Spasticity, Childhood-Onset, with Hyperglycinemia

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69 SNOMED-CT via HPO
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74 UMLS via Orphanet
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