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 53 71 13 69
Sepiapterin Reductase Deficiency 53 23 49 24 55 71 28
Spr Deficiency 53 23 49 24 55 71
Dopa-Responsive Dystonia Due to Sepiapterin Reductase Deficiency 24 55
Psychomotor Disorders 41 69
Motor and Cognitive Disorder Due to Sepiapterin Reductase Deficiency 71
Autosomal Recessive Sepiapterin Reductase-Deficient Drd 55
Sepiapterin Reductase Deficiency; Srd 53
Dopa-Responsive Hypersomnia 23
Sepiapterin Reductase 13
Drd Due to Srd 55
Dyt-Spr 23
Drdsprd 71
Srd 53
Spr 72

Characteristics:

Orphanet epidemiological data:

55
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:

53
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:

31
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 : 53 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 dystonia, and has symptoms including seizures, tremor and muscle weakness. An important gene associated with Dystonia, Dopa-Responsive, Due to Sepiapterin Reductase Deficiency is SPR (Sepiapterin Reductase). Affiliated tissues include testes.

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.

NIH Rare Diseases : 49 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

Genetics Home Reference : 24 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.

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 dystonia 10.1
3 cerebral palsy 9.9
4 cerebritis 9.9
5 hyperphenylalaninemia 9.9
6 tetrahydrobiopterin deficiency 9.9
7 hypersomnia 9.9
8 hypotonia 9.9
9 adrenoleukodystrophy 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:

53
Neurologic Central Nervous System:
ataxia
sleep disturbances
seizures
tremor
hypersomnolence
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:

55 31 (show all 35)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 seizures 55 31 occasional (7.5%) Occasional (29-5%) HP:0001250
2 tremor 55 31 frequent (33%) Frequent (79-30%) HP:0001337
3 muscle weakness 55 31 frequent (33%) Frequent (79-30%) HP:0001324
4 dystonia 55 31 Frequent (79-30%) HP:0001332
5 bradykinesia 55 31 frequent (33%) Frequent (79-30%) HP:0002067
6 ptosis 55 31 frequent (33%) Frequent (79-30%) HP:0000508
7 hyperhidrosis 55 31 frequent (33%) Frequent (79-30%) HP:0000975
8 intellectual disability 55 31 frequent (33%) Frequent (79-30%) HP:0001249
9 hyperreflexia 55 31 frequent (33%) Frequent (79-30%) HP:0001347
10 sleep disturbance 55 31 frequent (33%) Frequent (79-30%) HP:0002360
11 delayed speech and language development 55 31 frequent (33%) Frequent (79-30%) HP:0000750
12 microcephaly 55 31 occasional (7.5%) Occasional (29-5%) HP:0000252
13 cognitive impairment 55 31 frequent (33%) Frequent (79-30%) HP:0100543
14 growth delay 55 31 occasional (7.5%) Occasional (29-5%) HP:0001510
15 rigidity 55 31 frequent (33%) Frequent (79-30%) HP:0002063
16 cerebral palsy 55 31 occasional (7.5%) Occasional (29-5%) HP:0100021
17 abnormality of the nose 55 31 frequent (33%) Frequent (79-30%) HP:0000366
18 motor delay 55 31 frequent (33%) Frequent (79-30%) HP:0001270
19 drowsiness 55 31 frequent (33%) Frequent (79-30%) HP:0002329
20 oculogyric crisis 55 31 frequent (33%) Frequent (79-30%) HP:0010553
21 small for gestational age 55 31 occasional (7.5%) Occasional (29-5%) HP:0001518
22 limb hypertonia 55 31 frequent (33%) Frequent (79-30%) HP:0002509
23 muscular hypotonia of the trunk 55 31 frequent (33%) Frequent (79-30%) HP:0008936
24 hypomimic face 55 31 frequent (33%) Frequent (79-30%) HP:0000338
25 temperature instability 55 31 frequent (33%) Frequent (79-30%) HP:0005968
26 ataxia 31 HP:0001251
27 spasticity 31 HP:0001257
28 dysarthria 31 HP:0001260
29 behavioral abnormality 55 Frequent (79-30%)
30 global developmental delay 31 HP:0001263
31 aggressive behavior 31 HP:0000718
32 hyperactivity 31 HP:0000752
33 choreoathetosis 31 HP:0001266
34 oculomotor apraxia 31 HP:0000657
35 transient hyperphenylalaninemia 31 HP:0008297

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


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

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 28 SPR

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

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

38
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
Child neurology: paroxysmal stiffening, upward gaze, and hypotonia: hallmarks of sepiapterin reductase deficiency. ( 22291068 )
2012
3
Endothelium-specific sepiapterin reductase deficiency in DOCA-salt hypertension. ( 22467312 )
2012
4
Levodopa response reveals sepiapterin reductase deficiency in a female heterozygote with adrenoleukodystrophy. ( 23430877 )
2012
5
Sepiapterin reductase deficiency: a treatable mimic of cerebral palsy. ( 22522443 )
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
The silkworm mutant lemon (lemon lethal) is a potential insect model for human sepiapterin reductase deficiency. ( 19246455 )
2009
9
Sepiapterin reductase deficiency in a 2-year-old girl with incomplete response to treatment during short-term follow-up. ( 19130291 )
2009
10
Two Greek siblings with sepiapterin reductase deficiency. ( 18502672 )
2008
11
A murine model for human sepiapterin-reductase deficiency. ( 16532389 )
2006
12
Dopa-responsive hypersomnia and mixed movement disorder due to sepiapterin reductase deficiency. ( 17159114 )
2006
13
Sepiapterin reductase deficiency: clinical presentation and evaluation of long-term therapy. ( 17074599 )
2006
14
Sepiapterin reductase deficiency an autosomal recessive DOPA- responsive dystonia. ( 16650784 )
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:

71
# 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
# 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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