DRDSPRD
MCID: DYS161
MIFTS: 51

Dystonia, Dopa-Responsive, Due to Sepiapterin Reductase Deficiency (DRDSPRD)

Categories: Genetic diseases, Metabolic diseases, Neuronal diseases, Rare 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 44 73
Sepiapterin Reductase Deficiency 57 12 24 53 25 59 75 29 6 15 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 tetrahydrobiopterin deficiency, and has symptoms including seizures, ataxia and tremor. An important gene associated with Dystonia, Dopa-Responsive, Due to Sepiapterin Reductase Deficiency is SPR (Sepiapterin Reductase), and among its related pathways/superpathways are Metabolism and Regulation of cholesterol biosynthesis by SREBP (SREBF). 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 Jean Baptiste Point du Sable (before 1750 ? 1818) is honored as the first permanent non-Native-American... 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:

(show all 38)
# Related Disease Score Top Affiliating Genes
1 dystonia, dopa-responsive 31.8 GCH1 SPR
2 tetrahydrobiopterin deficiency 31.6 GCH1 QDPR SPR
3 hyperphenylalaninemia, bh4-deficient, a 31.5 GCH1 QDPR
4 hyperphenylalaninemia 29.9 GCH1 QDPR SPR
5 parkinson disease, late-onset 11.2
6 dopa-responsive dystonia; segawa syndrome ad 11.1
7 retinal detachment 10.3
8 dystonia 10.2
9 influenza 10.2
10 adrenoleukodystrophy 10.1
11 cerebral palsy 10.1
12 hypothyroidism 10.1
13 movement disease 10.1
14 growth hormone deficiency 10.1
15 hypotonia 10.1
16 hypersomnia 10.1
17 mumps 10.1
18 avian influenza 10.1
19 leishmaniasis 10.1
20 visceral leishmaniasis 10.1
21 methylmalonyl-coa epimerase deficiency 10.0
22 bipolar disorder 10.0
23 hyperphenylalaninemia, bh4-deficient, b 10.0 GCH1 QDPR
24 pityriasis rubra pilaris 9.9
25 neuroblastoma 9.9
26 welander distal myopathy 9.9
27 lipoprotein glomerulopathy 9.9
28 burns 9.9
29 insulinoma 9.9
30 rickets 9.9
31 peanut allergy 9.9
32 paraplegia 9.9
33 prion disease 9.9
34 appendicitis 9.9
35 herpes simplex 9.9
36 viral infectious disease 9.9
37 macrophagic myofasciitis 9.9
38 phenylketonuria 9.8 GCH1 QDPR

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 motor delay 59 32 frequent (33%) Frequent (79-30%) HP:0001270
15 rigidity 59 32 frequent (33%) Frequent (79-30%) HP:0002063
16 cerebral palsy 59 32 occasional (7.5%) Occasional (29-5%) HP:0100021
17 abnormality of the nose 59 32 frequent (33%) Frequent (79-30%) HP:0000366
18 bradykinesia 59 32 frequent (33%) Frequent (79-30%) HP:0002067
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:


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

MGI Mouse Phenotypes related to Dystonia, Dopa-Responsive, Due to Sepiapterin Reductase Deficiency:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 homeostasis/metabolism MP:0005376 9.23 GCH1 INSIG1 INSIG2 PDHA1 QDPR SCAP

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 21)
# Title Authors Year
1
Sepiapterin reductase deficiency: Report of 5 new cases. ( 28189489 )
2017
2
Dopamine-Responsive Growth-Hormone Deficiency and Central Hypothyroidism in Sepiapterin Reductase Deficiency. ( 26006722 )
2015
3
Urine sepiapterin excretion as a new diagnostic marker for sepiapterin reductase deficiency. ( 26123188 )
2015
4
Very early pattern of movement disorders in sepiapterin reductase deficiency. ( 24212389 )
2013
5
Sepiapterin reductase deficiency: a treatable mimic of cerebral palsy. ( 22522443 )
2012
6
Levodopa response reveals sepiapterin reductase deficiency in a female heterozygote with adrenoleukodystrophy. ( 23430877 )
2012
7
Endothelium-specific sepiapterin reductase deficiency in DOCA-salt hypertension. ( 22467312 )
2012
8
Child neurology: paroxysmal stiffening, upward gaze, and hypotonia: hallmarks of sepiapterin reductase deficiency. ( 22291068 )
2012
9
Genotype-phenotype correlations in sepiapterin reductase deficiency. A splicing defect accounts for a new phenotypic variant. ( 21431957 )
2011
10
Sepiapterin reductase deficiency: two Indian siblings with unusual clinical features. ( 20222129 )
2010
11
Sepiapterin reductase deficiency in a 2-year-old girl with incomplete response to treatment during short-term follow-up. ( 19130291 )
2009
12
The silkworm mutant lemon (lemon lethal) is a potential insect model for human sepiapterin reductase deficiency. ( 19246455 )
2009
13
Two Greek siblings with sepiapterin reductase deficiency. ( 18502672 )
2008
14
Sepiapterin reductase deficiency an autosomal recessive DOPA- responsive dystonia. ( 16650784 )
2006
15
Sepiapterin reductase deficiency: clinical presentation and evaluation of long-term therapy. ( 17074599 )
2006
16
A murine model for human sepiapterin-reductase deficiency. ( 16532389 )
2006
17
Dopa-responsive hypersomnia and mixed movement disorder due to sepiapterin reductase deficiency. ( 17159114 )
2006
18
Sepiapterin reductase deficiency: a congenital dopa-responsive motor and cognitive disorder. ( 16049044 )
2005
19
Detection of sepiapterin in CSF of patients with sepiapterin reductase deficiency. ( 11855937 )
2002
20
Tetrahydrobiopterin deficiencies without hyperphenylalaninemia: diagnosis and genetics of dopa-responsive dystonia and sepiapterin reductase deficiency. ( 11592814 )
2001
21
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 21)
# 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.655C> T (p.Arg219Ter) single nucleotide variant Pathogenic rs779204655 GRCh37 Chromosome 2, 73118535: 73118535
19 SPR NM_003124.4(SPR): c.655C> T (p.Arg219Ter) single nucleotide variant Pathogenic rs779204655 GRCh38 Chromosome 2, 72891406: 72891406
20 SPR NM_003124.4(SPR): c.596delG (p.Gly199Valfs) deletion Pathogenic GRCh38 Chromosome 2, 72891347: 72891347
21 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...

Cellular components related to Dystonia, Dopa-Responsive, Due to Sepiapterin Reductase Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 SREBP-SCAP-Insig complex GO:0032937 8.62 INSIG1 INSIG2

Biological processes related to Dystonia, Dopa-Responsive, Due to Sepiapterin Reductase Deficiency according to GeneCards Suite gene sharing:

(show all 19)
# Name GO ID Score Top Affiliating Genes
1 steroid metabolic process GO:0008202 9.65 INSIG1 INSIG2 SCAP
2 response to insulin GO:0032868 9.58 INSIG2 SCAP
3 roof of mouth development GO:0060021 9.58 INSIG1 INSIG2
4 cholesterol metabolic process GO:0008203 9.58 INSIG1 INSIG2 SCAP
5 inner ear morphogenesis GO:0042472 9.57 INSIG1 INSIG2
6 cellular amino acid metabolic process GO:0006520 9.56 QDPR SRR
7 cholesterol biosynthetic process GO:0006695 9.55 INSIG1 INSIG2
8 triglyceride metabolic process GO:0006641 9.54 INSIG1 INSIG2
9 sterol biosynthetic process GO:0016126 9.52 INSIG1 INSIG2
10 middle ear morphogenesis GO:0042474 9.51 INSIG1 INSIG2
11 negative regulation of fatty acid biosynthetic process GO:0045717 9.49 INSIG1 INSIG2
12 nitric oxide biosynthetic process GO:0006809 9.46 GCH1 SPR
13 cofactor metabolic process GO:0051186 9.43 GCH1 SPR
14 cranial suture morphogenesis GO:0060363 9.37 INSIG1 INSIG2
15 negative regulation of steroid biosynthetic process GO:0010894 9.32 INSIG1 INSIG2
16 response to sterol depletion GO:0006991 9.26 INSIG1 INSIG2
17 dihydrobiopterin metabolic process GO:0051066 9.16 GCH1 QDPR
18 tetrahydrobiopterin biosynthetic process GO:0006729 9.13 GCH1 QDPR SPR
19 SREBP signaling pathway GO:0032933 8.8 INSIG1 INSIG2 SCAP

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