Sepiapterin reductase deficiency
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
Age of Onset
Autosomal dominant ?A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease
Autosomal recessive ?Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype
X-linked dominant ?X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.
X-linked recessive ?Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder
Mitochondrial or multigenic ?Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.
Multigenic or multifactor ?Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.
Other Names (AKA)
SPR deficiency; DYT/PARK-SPR; Dopa-responsive dystonia due to sepiapterin reductase deficiency;
Congenital and Genetic Diseases; Metabolic disorders; Musculoskeletal Diseases;
Sepiapterin reductase deficiency is a neurometabolic disorder characterized by a pattern of involuntary sustained muscle contractions known as
- motor and speech delay
- hypotonia affecting the trunk and limbs (axial hypotonia)
dystonia(unusual body posturing or twisting movements that are caused by uncontrolled muscle contractions)
- oculogyric crises (abnormal rotation of the eyeballs; extreme irritability and agitation; and pain, muscle spasms, and uncontrolled movements, especially of the head and neck)
- parkinsonian signs (tremor, bradykinesia (slowness of mevement), masked facies, rigidity)
- limb hypertonia
- psychiatric and/or behavioral abnormalities (anxiety, irritability)
- autonomic dysfunction
- sleep disturbances (hypersomnia, difficulty initiating or maintaining sleep, and drowsiness)
This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.
|Medical Terms||Other Names||
|30%-79% of people have these symptoms|
|Abnormality of the nose||
Slowness of movements
[ more ]
Abnormality of cognition
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|Delayed speech and language development||
Deficiency of speech development
Delayed language development
Delayed speech acquisition
Delayed speech development
Impaired speech and language development
Impaired speech development
Language development deficit
Late-onset speech development
Poor language development
Speech and language delay
Speech and language difficulties
[ more ]
[ more ]
Dull facial expression
Mental retardation, nonspecific
[ more ]
Increased muscle tone of arm or leg
|Muscular hypotonia of the trunk||
Low muscle tone in trunk
Drooping upper eyelid
[ more ]
|5%-29% of people have these symptoms|
[ more ]
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference
[ more ]
|Small for gestational age||
Birth weight less than 10th percentile
Low birth weight
[ more ]
|Percent of people who have these symptoms is not available through HPO|
[ more ]
Difficulty articulating speech
|Global developmental delay||0001263|
More active than typical
Onset in first year of life
Onset in infancy
[ more ]
Involuntary muscle stiffness, contraction, or spasm
SPR gene mutations disrupt the production of sepiapterin reductase. This leads to a reduction or absence of tetrahydrobiopterin. Without tetrahydrobiopterin, the brain cannot produce dopamine and serotonin, leading to the symptoms of sepiapterin reductase deficiency.
Diagnosis is based on characteristic abnormalities of neurotransmitters and pterins in the cerebrospinal fluid. More specifically, cerebrospinal fluid findings include low levels of 5-hydroxyindolacetic acid (5-HIAA) and homovanillic acid (HVA); slightly increased levels of neopterin; and elevated total biopterin and dihydrobiopterin (BH2). Sepiapterin reductase activity in
- The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
- Orphanet lists international laboratories offering diagnostic testing for this condition.
Treatment should be started as soon as possible in order to avoid irreversible neurological damage and continued for life. The amounts of L-dopa administered to people with sepiapterin reductase deficiency vary, but, in general, tends to be between 0.1 and 16 mg/kg/day. 5-hydroxytryptophan doses tend to be between 0.14 to 6 mg/kg/day. Combination therapy is introduced slowly and increased by over the course of days or weeks until the final target concentration is reached. People receiving this treatment regimen require careful monitoring because increasing the dose too quickly can cause side-effects. Patients receiving treatment may be monitored with routine evaluations by a pediatric
If L-dopa and 5-hydroxytryptophan in combination with carbidopa are not well tolerated or don't achieve the desired results, other medications may be considered. These include monoamine oxidase inhibitors, serotonin reuptake inhibitors, melatonin, dopamine agonists, anticholinergics, and methylphenidate. While these medications address the motor abnormalities of the condition, cognitive delays commonly remain.
Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.
Conditions with similar signs and symptoms from Orphanet
Differential diagnoses include other forms of DRD such as autosomal recessive DRD and autosomal dominant DRD, infantile dystonia-parkinsonism, infantile-onset spastic paraplegia, some forms of epilepsy and cerebral palsy.
Visit the Orphanet disease page for more information.
Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.
These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.
- Genetics Home Reference (GHR) contains information on Sepiapterin reductase deficiency. This website is maintained by the National Library of Medicine.
- GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
- The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
- Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
- Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
- PubMed is a searchable database of medical literature and lists journal articles that discuss Sepiapterin reductase deficiency. Click on the link to view a sample search on this topic.
- B. G. R. Neville, R. Parascandalo, R. Farrugia and A. Felice, Sepiapterin reductase deficiency: a congenital dopa-responsive motor and cognitive disorder, Brain (2005) 128(10):2291-2296.
- Sepiapterin reductase deficiency. Genetics Home Reference (GHR). June 2011; https://ghr.nlm.nih.gov/condition/sepiapterin-reductase-deficiency.
- Kamm C. Dopa-responsive dystonia due to sepiapterin reductase deficiency. Orphanet. November 2013; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=70594.
- Friedman J. Sepiapterin Reductase Deficiency. GeneReviews. July 1, 2015; https://www.ncbi.nlm.nih.gov/books/NBK304122/.
- Echenne B et al.,. Sepiapterin reductase deficiency: Clinical presentation and evaluation of long-term therapy. Pediatric Neurology. 2006 Nov; 35(5):308-13. https://www.ncbi.nlm.nih.gov/pubmed/?term=17074599.