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

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OMIM 57 612716 Disease Ontology 12 DOID:0111168 MeSH 44 C562657 D004421 D011596 SNOMED-CT 68 45116002 Orphanet 59 ORPHA70594

UMLS via Orphanet 74 C0268468 ICD10 via Orphanet 34 G24.1 MedGen 42 C0268468 SNOMED-CT via HPO 69 263681008 258211005 271611007 248149005 128274005 72089000 11934000 193662007 248004009 61372001 162294008 229721007 29164008 62415009 44548000 161857006 312230002 364538006 415690000 415691001 52613005 228156007 247578003 91138005 128613002 246545002 313307000 84757009 91175000 85102008 221360009 397790002 8011004 224958001 43105007 26544005 26079004 86854008 276617005 444896005 59576002 267258002 276610007 16046003 399317006 271782001 79519003 53888004 28575006 5332004 128188000 386806002 more UMLS 73 C0268468 C0033922

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

Clinical features from OMIM:

612716

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