MCID: DYS161
MIFTS: 34

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 57 75 13 73
Sepiapterin Reductase Deficiency 57 12 24 53 25 59 75 29 6 40
Spr Deficiency 57 12 24 53 25 59 75
Dopa-Responsive Dystonia Due to Sepiapterin Reductase Deficiency 12 25 59
Psychomotor Disorders 44 73
Drd Due to Srd 12 59
Srd 57 12
Motor and Cognitive Disorder Due to Sepiapterin Reductase Deficiency 75
Autosomal Recessive Sepiapterin Reductase-Deficient Drd 59
Sepiapterin Reductase Deficiency; Srd 57
Dopa-Responsive Hypersomnia 24
Sepiapterin Reductase 13
Dyt-Spr 24
Drdsprd 75
Spr 76

Characteristics:

Orphanet epidemiological data:

59
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:

57
Inheritance:
autosomal recessive
?autosomal dominant

Miscellaneous:
onset in infancy
variable severity
defect in tetrahydrobiopterin (bh4) synthesis
later onset has been reported
treatment with bh4 is effective
neurotransmitter treatment with l-dopa and serotonin or precursors is effective
early treatment can reduce neurologic symptoms
symptoms benefit from sleep
marked favorable response to l-dopa treatment
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 : 57 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 and movement disease, and has symptoms including lethargy, neurobehavioral manifestations and psychomotor skills impaired. An important gene associated with Dystonia, Dopa-Responsive, Due to Sepiapterin Reductase Deficiency is SPR (Sepiapterin Reductase). Affiliated tissues include testes, and related phenotypes are ptosis and hyperhidrosis

Disease Ontology : 12 A dystonia characterized by sustained muscle contractions with diurnal fluctuations, axial hypotonia, oculogyric crises, delays in motor and cognitive development and severe dopamine and serotonin deficiencies that has material basis in mutation in the SPR gene on chromosome 2p resulting in sepiapterin reductase deficiency.

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 : 53 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.

UniProtKB/Swiss-Prot : 75 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 : 76 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:

# Related Disease Score Top Affiliating Genes
1 dystonia, dopa-responsive 11.0
2 movement disease 10.1
3 dystonia 10.1
4 adrenoleukodystrophy 9.9
5 cerebral palsy 9.9
6 cerebritis 9.9
7 hyperphenylalaninemia 9.9
8 tetrahydrobiopterin deficiency 9.9
9 hypersomnia 9.9
10 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:

57
Neurologic Central Nervous System:
seizures
ataxia
spasticity
dysarthria
tremor
more
Neurologic Behavioral Psychiatric Manifestations:
aggressive behavior
hyperactivity

Growth Other:
growth retardation

Head And Neck Head:
microcephaly

Head And Neck Eyes:
oculomotor apraxia
oculogyric crises

Laboratory Abnormalities:
decreased homovanillic acid (hva) in csf
transient hyperphenylalaninemia occurs on oral loading test with phenylalanine
sepiapterin reductase deficiency (fibroblasts)
decreased 5-hydroxyindoleacetic acid (5-hiaa) in csf
elevated sepiapterin in csf
more

Clinical features from OMIM:

612716

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

59 32 (show all 35)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 ptosis 59 32 frequent (33%) Frequent (79-30%) HP:0000508
2 hyperhidrosis 59 32 frequent (33%) Frequent (79-30%) HP:0000975
3 intellectual disability 59 32 frequent (33%) Frequent (79-30%) HP:0001249
4 seizures 59 32 occasional (7.5%) Occasional (29-5%) HP:0001250
5 muscle weakness 59 32 frequent (33%) Frequent (79-30%) HP:0001324
6 tremor 59 32 frequent (33%) Frequent (79-30%) HP:0001337
7 hyperreflexia 59 32 frequent (33%) Frequent (79-30%) HP:0001347
8 sleep disturbance 59 32 frequent (33%) Frequent (79-30%) HP:0002360
9 delayed speech and language development 59 32 frequent (33%) Frequent (79-30%) HP:0000750
10 microcephaly 59 32 occasional (7.5%) Occasional (29-5%) HP:0000252
11 cognitive impairment 59 32 frequent (33%) Frequent (79-30%) HP:0100543
12 growth delay 59 32 occasional (7.5%) Occasional (29-5%) HP:0001510
13 dystonia 59 32 Frequent (79-30%) HP:0001332
14 rigidity 59 32 frequent (33%) Frequent (79-30%) HP:0002063
15 cerebral palsy 59 32 occasional (7.5%) Occasional (29-5%) HP:0100021
16 abnormality of the nose 59 32 frequent (33%) Frequent (79-30%) HP:0000366
17 bradykinesia 59 32 frequent (33%) Frequent (79-30%) HP:0002067
18 motor delay 59 32 frequent (33%) Frequent (79-30%) HP:0001270
19 hypomimic face 59 32 frequent (33%) Frequent (79-30%) HP:0000338
20 drowsiness 59 32 frequent (33%) Frequent (79-30%) HP:0002329
21 oculogyric crisis 59 32 frequent (33%) Frequent (79-30%) HP:0010553
22 small for gestational age 59 32 occasional (7.5%) Occasional (29-5%) HP:0001518
23 limb hypertonia 59 32 frequent (33%) Frequent (79-30%) HP:0002509
24 muscular hypotonia of the trunk 59 32 frequent (33%) Frequent (79-30%) HP:0008936
25 temperature instability 59 32 frequent (33%) Frequent (79-30%) HP:0005968
26 ataxia 32 HP:0001251
27 spasticity 32 HP:0001257
28 dysarthria 32 HP:0001260
29 behavioral abnormality 59 Frequent (79-30%)
30 global developmental delay 32 HP:0001263
31 aggressive behavior 32 HP:0000718
32 choreoathetosis 32 HP:0001266
33 oculomotor apraxia 32 HP:0000657
34 hyperactivity 32 HP:0000752
35 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:

# Genetic test Affiliating Genes
1 Sepiapterin Reductase Deficiency 29 SPR

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

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

41
Testes

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

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

(show all 18)
# Title Authors Year
1
Very early pattern of movement disorders in sepiapterin reductase deficiency. ( 24212389 )
2013
2
Sepiapterin reductase deficiency: a treatable mimic of cerebral palsy. ( 22522443 )
2012
3
Levodopa response reveals sepiapterin reductase deficiency in a female heterozygote with adrenoleukodystrophy. ( 23430877 )
2012
4
Endothelium-specific sepiapterin reductase deficiency in DOCA-salt hypertension. ( 22467312 )
2012
5
Child neurology: paroxysmal stiffening, upward gaze, and hypotonia: hallmarks of sepiapterin reductase deficiency. ( 22291068 )
2012
6
Genotype-phenotype correlations in sepiapterin reductase deficiency. A splicing defect accounts for a new phenotypic variant. ( 21431957 )
2011
7
Sepiapterin reductase deficiency: two Indian siblings with unusual clinical features. ( 20222129 )
2010
8
Sepiapterin reductase deficiency in a 2-year-old girl with incomplete response to treatment during short-term follow-up. ( 19130291 )
2009
9
The silkworm mutant lemon (lemon lethal) is a potential insect model for human sepiapterin reductase deficiency. ( 19246455 )
2009
10
Two Greek siblings with sepiapterin reductase deficiency. ( 18502672 )
2008
11
Sepiapterin reductase deficiency an autosomal recessive DOPA- responsive dystonia. ( 16650784 )
2006
12
Sepiapterin reductase deficiency: clinical presentation and evaluation of long-term therapy. ( 17074599 )
2006
13
A murine model for human sepiapterin-reductase deficiency. ( 16532389 )
2006
14
Dopa-responsive hypersomnia and mixed movement disorder due to sepiapterin reductase deficiency. ( 17159114 )
2006
15
Sepiapterin reductase deficiency: a congenital dopa-responsive motor and cognitive disorder. ( 16049044 )
2005
16
Detection of sepiapterin in CSF of patients with sepiapterin reductase deficiency. ( 11855937 )
2002
17
Tetrahydrobiopterin deficiencies without hyperphenylalaninemia: diagnosis and genetics of dopa-responsive dystonia and sepiapterin reductase deficiency. ( 11592814 )
2001
18
Sepiapterin Reductase Deficiency ( 26131547 )
1993

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

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

75
# 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
(show all 19)
# 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.355C> T (p.Gln119Ter) single nucleotide variant Pathogenic rs121917746 GRCh38 Chromosome 2, 72888364: 72888364
3 SPR NM_003124.4(SPR): c.448_452delAGAAC (p.Thr151Glyfs) deletion Pathogenic rs587776777 GRCh37 Chromosome 2, 73115586: 73115590
4 SPR NM_003124.4(SPR): c.448_452delAGAAC (p.Thr151Glyfs) deletion Pathogenic rs587776777 GRCh38 Chromosome 2, 72888457: 72888461
5 SPR NM_003124.4(SPR): c.448A> G (p.Arg150Gly) single nucleotide variant Pathogenic rs104893665 GRCh37 Chromosome 2, 73115586: 73115586
6 SPR NM_003124.4(SPR): c.448A> G (p.Arg150Gly) single nucleotide variant Pathogenic rs104893665 GRCh38 Chromosome 2, 72888457: 72888457
7 SPR SPR, -13G-A single nucleotide variant Pathogenic
8 SPR NM_003124.4(SPR): c.488C> T (p.Pro163Leu) single nucleotide variant Pathogenic rs104893666 GRCh37 Chromosome 2, 73115626: 73115626
9 SPR NM_003124.4(SPR): c.488C> T (p.Pro163Leu) single nucleotide variant Pathogenic rs104893666 GRCh38 Chromosome 2, 72888497: 72888497
10 SPR NM_003124.4(SPR): c.751A> T (p.Lys251Ter) single nucleotide variant Pathogenic rs121917747 GRCh37 Chromosome 2, 73118631: 73118631
11 SPR NM_003124.4(SPR): c.751A> T (p.Lys251Ter) single nucleotide variant Pathogenic rs121917747 GRCh38 Chromosome 2, 72891502: 72891502
12 SPR NM_003124.4(SPR): c.304G> T (p.Gly102Cys) single nucleotide variant Pathogenic rs387907200 GRCh37 Chromosome 2, 73114865: 73114865
13 SPR NM_003124.4(SPR): c.304G> T (p.Gly102Cys) single nucleotide variant Pathogenic rs387907200 GRCh38 Chromosome 2, 72887736: 72887736
14 SPR NM_003124.4(SPR): c.596-2A> G single nucleotide variant Pathogenic rs398122922 GRCh37 Chromosome 2, 73118474: 73118474
15 SPR NM_003124.4(SPR): c.596-2A> G single nucleotide variant Pathogenic rs398122922 GRCh38 Chromosome 2, 72891345: 72891345
16 SPR NM_003124.4(SPR): c.106G> A (p.Val36Met) single nucleotide variant Uncertain significance rs869312688 GRCh37 Chromosome 2, 73114667: 73114667
17 SPR NM_003124.4(SPR): c.106G> A (p.Val36Met) single nucleotide variant Uncertain significance rs869312688 GRCh38 Chromosome 2, 72887538: 72887538
18 SPR NM_003124.4(SPR): c.596delG (p.Gly199Valfs) deletion Pathogenic GRCh38 Chromosome 2, 72891347: 72891347
19 SPR NM_003124.4(SPR): c.596delG (p.Gly199Valfs) deletion Pathogenic GRCh37 Chromosome 2, 73118476: 73118476

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...

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