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

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Disease Ontology 12 DOID:0111168 OMIM 58 612716 MeSH 45 C562657 D004421 D011596 SNOMED-CT 69 45116002 ICD10 via Orphanet 35 G24.1

UMLS via Orphanet 75 C0268468 Orphanet 60 ORPHA70594 MedGen 43 C0268468 SNOMED-CT via HPO 70 11934000 128188000 128274005 128613002 16046003 161857006 162294008 193662007 221360009 224958001 228156007 229721007 246545002 247578003 248004009 248149005 258211005 26079004 263681008 26544005 267258002 271611007 271782001 276610007 276617005 28575006 29164008 312230002 313307000 364538006 386806002 397790002 399317006 415690000 415691001 43105007 444896005 44548000 52613005 5332004 53888004 59576002 61372001 62415009 72089000 79519003 8011004 84757009 85102008 86854008 91138005 91175000 more UMLS 74 C0033922 C0268468

OMIM : ⁵⁸ 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 tetrahydrobiopterin deficiency and dystonia, dopa-responsive, 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 heart, 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 : ²⁶ 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 : ⁵⁴ 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 : ⁷⁶ 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.

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GeneReviews: NBK304122

Clinical features from OMIM:

612716

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