Dopa-responsive dystonia due to sepiapterin reductase deficiency

General Information (adopted from Orphanet):

Synonyms, Signs: sepiapterin reductase deficiency
DRD due to SRD
DRD autosomique récessive par déficit en sépiaptérine réductase
Autosomal recessive sepiapterin reductase-deficient DRD
spr deficiency
Number of Symptoms 66
OrphanetNr: 70594
OMIM Id: 612716
ICD-10: G24.1
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: 43 cases
Inheritance:
Age of onset:

Disease classification (adopted from Orphanet):

Parent Diseases: Disorder of pterin metabolism
 -Rare genetic disease
Dopa-responsive dystonia
 -Rare genetic disease
 -Rare neurologic disease

Comment:

gene: SPR The major difference between GCH1 deficiency and SPR deficiency lies in the CSF levels of biopterin. These levels are apparently elevated in SPR deficiency and generally decreased in GCH1 deficiency (PMID: 16650784). The variability in occurrence and severity of other symptoms of the condition, a.o. hypotonia, ataxia, tremors, spasticity, bulbar involvement, oculogyric crises, and cognitive impairment, is comparable with autosomal dominant GTPCH and tyrosine hydroxylase defciency, which are both classifed as forms of DOPA-responsive dystonia (PMID: 16650784).

Symptom Information: Sort by abundance 

1
 (HPO:0000858) Menstrual irregularities 22522443 IBIS 42 / 7739
2
 (HPO:0003110) Abnormality of urine homeostasis 22522443 IBIS 9 / 7739
3
 (HPO:0012384) Rhinitis 22522443 IBIS 18 / 7739
4
 (HPO:0002307) Drooling 22522443 IBIS 43 / 7739
5
 (HPO:0000252) Microcephaly 22522443 IBIS 832 / 7739
6
 (HPO:0000486) Strabismus 22522443 IBIS 576 / 7739
7
 (HPO:0000639) Nystagmus 22522443 IBIS 555 / 7739
8
 (HPO:0000496) Abnormality of eye movement 22522443 IBIS 79 / 7739
9
 (HPO:0000657) Oculomotor apraxia 22522443 IBIS 54 / 7739
10
 (HPO:0000508) Ptosis 22522443 IBIS 459 / 7739
11
 (HPO:0000518) Cataract 22522443 IBIS 454 / 7739
12
 (HPO:0002329) Drowsiness 22522443 IBIS 19 / 7739
13
 (HPO:0001249) Intellectual disability 16049044; 22522443 IBIS 1089 / 7739
14
 (HPO:0001257) Spasticity 16650784 IBIS 251 / 7739
15
 (HPO:0001270) Motor delay 23430877 IBIS 322 / 7739
16
 (HPO:0000722) Obsessive-compulsive behavior 22522443 IBIS 35 / 7739
17
 (HPO:0002015) Dysphagia 22522443 IBIS 301 / 7739
18
 (HPO:0012049) Laryngeal dystonia 22522443 IBIS 7 / 7739
19
 (HPO:0001266) Choreoathetosis 16049044; 22522443 IBIS 57 / 7739
20
 (HPO:0002548) Parkinsonism with favorable response to dopaminergic medication 22522443 IBIS 13 / 7739
21
 (HPO:0001265) Hyporeflexia 22522443 IBIS 208 / 7739
22
 (HPO:0002360) Sleep disturbance 22522443 IBIS 113 / 7739
23
 (HPO:0000739) Anxiety 22522443 IBIS 67 / 7739
24
 (HPO:0001263) Global developmental delay 16650784 IBIS 853 / 7739
25
 (HPO:0002067) Bradykinesia 22522443 IBIS 62 / 7739
26
 (HPO:0001337) Tremor 16049044; 22522443 IBIS 200 / 7739
27
 (HPO:0100786) Hypersomnia 24588500 IBIS 4 / 7739
28
 (HPO:0002063) Rigidity 22522443 IBIS 92 / 7739
29
 (HPO:0001250) Seizures 22522443 IBIS 1245 / 7739
30
 (HPO:0002591) Polyphagia 22522443 IBIS 25 / 7739
31
 (HPO:0000716) Depression 22522443 IBIS 99 / 7739
32
 (HPO:0000752) Hyperactivity 22522443 IBIS 140 / 7739
33
 (HPO:0000737) Irritability 22522443 IBIS 93 / 7739
34
 (HPO:0100710) Impulsivity 22522443 IBIS 16 / 7739
35
 (HPO:0010553) Oculogyric crisis 24588500; 22522443 IBIS 5 / 7739
36
 (HPO:0002921) Abnormality of the cerebrospinal fluid 24588500 IBIS 6 / 7739
37
 (HPO:0003785) Decreased CSF homovanillic acid 24588500; 16650784 IBIS 7 / 7739
38
 (HPO:0001336) Myoclonus 22522443 IBIS 115 / 7739
39
 (HPO:0001332) Dystonia 24588500; 16650784 IBIS 197 / 7739
40
 (HPO:0001251) Ataxia 16650784 IBIS 413 / 7739
41
 (HPO:0001260) Dysarthria 23430877; 22522443 IBIS 329 / 7739
42
 (HPO:0001347) Hyperreflexia 22522443 IBIS 363 / 7739
43
 (HPO:0000718) Aggressive behavior 22522443 IBIS 109 / 7739
44
 (HPO:0000870) Prolactin excess 24588500 IBIS 10 / 7739
45
 (HPO:0002650) Scoliosis 22522443 IBIS 705 / 7739
46
 (HPO:0002572) Episodic vomiting 22522443 IBIS 12 / 7739
47
 (HPO:0002019) Constipation 22522443 IBIS 194 / 7739
48
 (HPO:0001510) Growth delay 22522443 IBIS 295 / 7739
49
 (HPO:0001508) Failure to thrive 22522443 IBIS 454 / 7739
50
 (HPO:0000975) Hyperhidrosis 22522443 IBIS 64 / 7739
51
 (HPO:0002216) Premature graying of hair 22522443 IBIS 43 / 7739
52
 (HPO:0005968) Temperature instability 22522443 IBIS 5 / 7739
53
 (HPO:0008297) Transient hyperphenylalaninemia 16650784; 22522443 IBIS 4 / 7739
54
 (HPO:0008936) Muscular hypotonia of the trunk 16650784 IBIS 77 / 7739
55
 (OMIM) Elevated dihydrobiopterin in CSF 24588500 IBIS 1 / 7739
56
 (OMIM) Autonomic signs 22522443 IBIS 1 / 7739
57
 (OMIM) Decreased 5-hydroxyindoleacetic acid (5-HIAA) in CSF 24588500; 16650784 IBIS 1 / 7739
58
 (MedDRA:10047924) Wheezing 22522443 IBIS 8 / 7739
59
 (OMIM) Sepiapterin reductase deficiency (fibroblasts) 23430877 IBIS 1 / 7739
60
 (OMIM) Elevated biopterin in CSF 16650784 IBIS 1 / 7739
61
 (OMIM) Elevated sepiapterin in CSF 24588500; 16650784 IBIS 1 / 7739
62
 (OMIM) Decreased urinary HVA, 5-HIAA, and vanillyl mandelic acid (VMA) 22522443 IBIS 1 / 7739
63
 (HPO:0002483) Bulbar signs 16049044 IBIS 9 / 7739
64
 (OMIM) No hyperphenylalaninemia 16650784 IBIS 1 / 7739
65
 (OMIM) Normal urinary pterins 16650784 IBIS 1 / 7739
66
 (MedDRA:10013510) Disturbances in initiating and maintaining sleep 22522443 IBIS 1 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) 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 ...
Diagnosis OMIM Friedman et al. (2012) presented a diagnostic algorithm for patients with a possible disorder of neurotransmitter metabolism. They emphasized the importance of correct and early diagnosis of SPR deficiency since treatment with L-DOPA can offer substantial clinical improvement. ...
Clinical Description OMIM Bonafe et al. (2001) reported 2 patients with progressive psychomotor retardation, dystonia, severe dopamine and serotonin deficiencies (low levels of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA), respectively), and abnormal pterin pattern (high levels of biopterin and dihydrobiopterin) ...
Genotype-Phenotype Correlations OMIM In a Spanish boy with the classic infantile onset of neurologic symptoms due to SPR deficiency, Arrabal et al. (2011) identified a homozygous truncating mutation in the SPR gene (K251X; 182125.0006). Three sisters from a different Spanish family ...
Molecular genetics OMIM In 2 patients with SPR deficiency and neurologic features, Bonafe et al. (2001) identified homozygous (182125.0001) and compound heterozygous (182125.0002; 182125.0003) mutations in the SPR gene. The authors suggested that autosomal recessive deficiency of sepiapterin reductase leads to ...
Population genetics OMIM In 7 Maltese patients with classic features of SPR deficiency. Neville et al. (2005) identified a homozygous splice site mutation in the SPR gene (182125.0008). The authors postulated a founder effect in this population.

Friedman et ...