MCID: DYS161
MIFTS: 30

Dystonia, Dopa-Responsive, Due to Sepiapterin Reductase Deficiency

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

Aliases & Classifications for Dystonia, Dopa-Responsive, Due to Sepiapterin Reductase...

MalaCards integrated aliases for Dystonia, Dopa-Responsive, Due to Sepiapterin Reductase Deficiency:

Name: Dystonia, Dopa-Responsive, Due to Sepiapterin Reductase Deficiency 54 71 13 69
Sepiapterin Reductase Deficiency 23 50 24 25 56 71 29
Spr Deficiency 23 50 24 25 56 71
Dopa-Responsive Dystonia Due to Sepiapterin Reductase Deficiency 24 25 56
Psychomotor Disorders 42 69
Motor and Cognitive Disorder Due to Sepiapterin Reductase Deficiency 71
Autosomal Recessive Sepiapterin Reductase-Deficient Drd 56
Dopa-Responsive Hypersomnia 23
Sepiapterin Reductase 13
Drd Due to Srd 56
Dyt-Spr 23
Drdsprd 71

Characteristics:

Orphanet epidemiological data:

56
dopa-responsive dystonia due to sepiapterin reductase deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal; Age of death: normal life expectancy;

OMIM:

54
Inheritance:
autosomal recessive
?autosomal dominant

Miscellaneous:
onset in infancy
variable severity
later onset has been reported
symptoms benefit from sleep
defect in tetrahydrobiopterin (bh4) synthesis
marked favorable response to l-dopa treatment
treatment with bh4 is effective
neurotransmitter treatment with l-dopa and serotonin or precursors is effective
early treatment can reduce neurologic symptoms
a heterozygous mutation resulting in haploinsufficiency has been reported in 1 patient


HPO:

32
dystonia, dopa-responsive, due to sepiapterin reductase deficiency:
Onset and clinical course variable expressivity infantile onset
Inheritance autosomal recessive inheritance autosomal dominant inheritance


Classifications:



Summaries for Dystonia, Dopa-Responsive, Due to Sepiapterin Reductase...

OMIM : 54
SPR deficiency results in neurologic deterioration due to severe dopamine and serotonin deficiencies in the central nervous system caused by a defect in BH4 synthesis. Clinically, affected individuals show an L-DOPA-responsive, diurnally fluctuating movement disorder usually associated with cognitive delay and severe neurologic dysfunction. BH4 is a required cofactor for the synthesis of the neurotransmitters dopamine and serotonin. BH4 is also a required cofactor for phenylalanine hydroxylase (PAH; 612349), but patients with SPR deficiency do not exhibit overt hyperphenylalaninemia. The lack of hyperphenylalaninemia distinguishes SPR deficiency from other disorders of BH4 synthesis (see, e.g., HPABH4A, 261640). However, the neurologic phenotype of SPR deficiency resembles the other BH4-deficient disorders (summary by Bonafe et al., 2001 and Friedman et al., 2012). Another form of dopa-responsive dystonia (DTY5; 128230) is caused by mutation in the gene encoding GTP cyclohydrolase I (GCH1; 600225), which is also a component of the biopterin synthetic pathway. (612716)

MalaCards based summary : Dystonia, Dopa-Responsive, Due to Sepiapterin Reductase Deficiency, also known as sepiapterin reductase deficiency, is related to dystonia, dopa-responsive, with or without hyperphenylalaninemia and dystonia, and has symptoms including dystonia, dysarthria and ataxia. An important gene associated with Dystonia, Dopa-Responsive, Due to Sepiapterin Reductase Deficiency is SPR (Sepiapterin Reductase (7,8-Dihydrobiopterin:NADP+ Oxidoreductase)). Affiliated tissues include testes.

Genetics Home Reference : 25 Sepiapterin reductase deficiency is a condition characterized by movement problems, most often a pattern of involuntary, sustained muscle contractions known as dystonia. Other movement problems can include muscle stiffness (spasticity), tremors, problems with coordination and balance (ataxia), and involuntary jerking movements (chorea). People with sepiapterin reductase deficiency can experience episodes called oculogyric crises. These episodes involve abnormal rotation of the eyeballs; extreme irritability and agitation; and pain, muscle spasms, and uncontrolled movements, especially of the head and neck. Movement abnormalities are often worse late in the day. Most affected individuals have delayed development of motor skills such as sitting and crawling, and they typically are not able to walk unassisted. The problems with movement tend to worsen over time.

NIH Rare Diseases : 50 sepiapterin reductase deficiency is a neurometabolic disorder characterized by a pattern of involuntary sustained muscle contractions known as dystonia. other common features include axial hypotonia , oculogyric crises, and delays in motor and cognitive development. the condition is caused by mutations in the spr gene. it is inherited in an autosomal recessive fashion. treatment with levodopa (l-dopa) in combination with carbidopa has shown much success causing drastic improvements in motor functioning. last updated: 4/19/2016

UniProtKB/Swiss-Prot : 71 Dystonia, DOPA-responsive, due to sepiapterin reductase deficiency: A form of DOPA-responsive dystonia. In the majority of cases, patients manifest progressive psychomotor retardation, dystonia and spasticity. Cognitive anomalies are also often present. The disease is due to severe dopamine and serotonin deficiencies in the central nervous system caused by a defect in BH4 synthesis. Dystonia is defined by the presence of sustained involuntary muscle contractions, often leading to abnormal postures.

Wikipedia : 72 Sepiapterin reductase deficiency is an inherited pediatric disorder characterized by movement problems,... more...

GeneReviews: NBK304122

Related Diseases for Dystonia, Dopa-Responsive, Due to Sepiapterin Reductase...

Diseases related to Dystonia, Dopa-Responsive, Due to Sepiapterin Reductase Deficiency via text searches within MalaCards or GeneCards Suite gene sharing:

id Related Disease Score Top Affiliating Genes
1 dystonia, dopa-responsive, with or without hyperphenylalaninemia 11.2
2 dystonia 10.0
3 adrenoleukodystrophy 9.9
4 cerebral palsy 9.9
5 cerebritis 9.9
6 hyperphenylalaninemia 9.9
7 tetrahydrobiopterin deficiency 9.9
8 hypersomnia 9.9
9 hypotonia 9.9

Graphical network of the top 20 diseases related to Dystonia, Dopa-Responsive, Due to Sepiapterin Reductase Deficiency:



Diseases related to Dystonia, Dopa-Responsive, Due to Sepiapterin Reductase Deficiency

Symptoms & Phenotypes for Dystonia, Dopa-Responsive, Due to Sepiapterin Reductase...

Symptoms via clinical synopsis from OMIM:

54

Neurologic- Central Nervous System:
delayed psychomotor development
dysarthria
ataxia
tremor
spasticity
more
Head And Neck- Head:
microcephaly

Neurologic- Behavioral Psychiatric Manifestations:
hyperactivity
aggressive behavior

Growth- Other:
growth retardation

Head And Neck- Eyes:
oculomotor apraxia
oculogyric crises

Laboratory- Abnormalities:
sepiapterin reductase deficiency (fibroblasts)
decreased 5-hydroxyindoleacetic acid (5-hiaa) in csf
decreased homovanillic acid (hva) in csf
elevated sepiapterin in csf
elevated biopterin in csf
more

Clinical features from OMIM:

612716

Human phenotypes related to Dystonia, Dopa-Responsive, Due to Sepiapterin Reductase Deficiency:

32 (show all 17)
id Description HPO Frequency HPO Source Accession
1 dystonia 32 HP:0001332
2 dysarthria 32 HP:0001260
3 ataxia 32 HP:0001251
4 tremor 32 HP:0001337
5 spasticity 32 HP:0001257
6 choreoathetosis 32 HP:0001266
7 seizures 32 HP:0001250
8 microcephaly 32 HP:0000252
9 oculomotor apraxia 32 HP:0000657
10 global developmental delay 32 HP:0001263
11 intellectual disability 32 HP:0001249
12 hyperactivity 32 HP:0000752
13 aggressive behavior 32 HP:0000718
14 growth delay 32 HP:0001510
15 sleep disturbance 32 HP:0002360
16 muscular hypotonia of the trunk 32 HP:0008936
17 transient hyperphenylalaninemia 32 HP:0008297

UMLS symptoms related to Dystonia, Dopa-Responsive, Due to Sepiapterin Reductase Deficiency:


lethargy, neurobehavioral manifestations, psychomotor skills impaired, ataxia, dystonia, muscle spasticity, seizures, sleep disturbances, tremor, hypersomnolence

Drugs & Therapeutics for Dystonia, Dopa-Responsive, Due to Sepiapterin Reductase...

Search Clinical Trials , NIH Clinical Center for Dystonia, Dopa-Responsive, Due to Sepiapterin Reductase Deficiency

Cochrane evidence based reviews: psychomotor disorders

Genetic Tests for Dystonia, Dopa-Responsive, Due to Sepiapterin Reductase...

Genetic tests related to Dystonia, Dopa-Responsive, Due to Sepiapterin Reductase Deficiency:

id Genetic test Affiliating Genes
1 Sepiapterin Reductase Deficiency 29
2 Dopa-Responsive Dystonia Due to Sepiapterin Reductase Deficiency 24 SPR

Anatomical Context for Dystonia, Dopa-Responsive, Due to Sepiapterin Reductase...

MalaCards organs/tissues related to Dystonia, Dopa-Responsive, Due to Sepiapterin Reductase Deficiency:

39
Testes

Publications for Dystonia, Dopa-Responsive, Due to Sepiapterin Reductase...

Variations for Dystonia, Dopa-Responsive, Due to Sepiapterin Reductase...

UniProtKB/Swiss-Prot genetic disease variations for Dystonia, Dopa-Responsive, Due to Sepiapterin Reductase Deficiency:

71
id Symbol AA change Variation ID SNP ID
1 SPR p.Arg150Gly VAR_058007 rs104893665
2 SPR p.Pro163Leu VAR_058008 rs104893666

ClinVar genetic disease variations for Dystonia, Dopa-Responsive, Due to Sepiapterin Reductase Deficiency:

6
id Gene Variation Type Significance SNP ID Assembly Location
1 SPR NM_003124.4(SPR): c.355C> T (p.Gln119Ter) single nucleotide variant Pathogenic rs121917746 GRCh37 Chromosome 2, 73115493: 73115493
2 SPR NM_003124.4(SPR): c.448_452delAGAAC (p.Thr151Glyfs) deletion Pathogenic rs587776777 GRCh37 Chromosome 2, 73115586: 73115590
3 SPR NM_003124.4(SPR): c.448A> G (p.Arg150Gly) single nucleotide variant Pathogenic rs104893665 GRCh37 Chromosome 2, 73115586: 73115586
4 SPR SPR, -13G-A single nucleotide variant Pathogenic
5 SPR NM_003124.4(SPR): c.488C> T (p.Pro163Leu) single nucleotide variant Pathogenic rs104893666 GRCh37 Chromosome 2, 73115626: 73115626
6 SPR NM_003124.4(SPR): c.751A> T (p.Lys251Ter) single nucleotide variant Pathogenic rs121917747 GRCh37 Chromosome 2, 73118631: 73118631
7 SPR NM_003124.4(SPR): c.304G> T (p.Gly102Cys) single nucleotide variant Pathogenic rs387907200 GRCh37 Chromosome 2, 73114865: 73114865
8 SPR NM_003124.4(SPR): c.596-2A> G single nucleotide variant Pathogenic rs398122922 GRCh37 Chromosome 2, 73118474: 73118474

Expression for Dystonia, Dopa-Responsive, Due to Sepiapterin Reductase...

Search GEO for disease gene expression data for Dystonia, Dopa-Responsive, Due to Sepiapterin Reductase Deficiency.

Pathways for Dystonia, Dopa-Responsive, Due to Sepiapterin Reductase...

GO Terms for Dystonia, Dopa-Responsive, Due to Sepiapterin Reductase...

Sources for Dystonia, Dopa-Responsive, Due to Sepiapterin Reductase...

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