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Genetic and Rare Diseases Information Center (GARD)

Sepiapterin reductase deficiency

Other Names for this Disease
  • SPR deficiency
Related Diseases
See Disclaimer regarding information on this site. Some links on this page may take you to organizations outside of the National Institutes of Health.

Your Question

My child has been diagnosed with sepiapterin reductase deficiency. What is this condition? How is it treated? How long does it take for the effects of treatment with levodopa to become noticeable?

Our Answer

We have identified the following information that we hope you find helpful. If you still have questions, please contact us.

What is sepiapterin reductase deficiency?

Sepiapterin reductase deficiency is a type of neurotransmitter disorder. It can also be more broadly classified as an inborn error of metabolism, because it is caused by an error in the pterin metabolism. Pterin metabolism plays an important role in making neurotransmitters in the brain, specifically dopamine, serotonin, biopterin, and their metabolites.[1] This deficiency is caused by mutations in the SPR gene and is inherited in an autosomal recessive fashion. Common symptoms include developmental delay, learning disability, and impaired motor skills.[1] Treatment with levodopa has shown much success causing drastic improvements in motor functioning.[1]
Last updated: 2/18/2009

What are inborn errors of metabolism?

Our bodies get the energy they need from food through metabolism, the chemical reactions in the body's cells that convert the fuel from food into the energy needed to do everything from moving to thinking to growing. Specific proteins in the body control the chemical reactions of metabolism, and each chemical reaction is coordinated with other body functions.[2]

In a broad sense, a metabolic disorder is any disease that is caused by an abnormal chemical reaction in the body's cells. Most disorders of metabolism involve either abnormal levels of enzymes or hormones or problems with the functioning of those enzymes or hormones. When the metabolism of body chemicals is blocked or defective, it can cause a buildup of toxic substances in the body or a deficiency of substances needed for normal body function, either of which can lead to serious symptoms.[2] Some metabolic diseases are inherited and these conditions are called inborn errors of metabolism.[2]
Last updated: 2/18/2009

What causes sepiapterin reductase deficiency?

Sepiapterin reductase deficiency is caused by a mutation in the SPR gene.
Last updated: 2/18/2009

What are the symptoms of sepiapterin reductase deficiency?

Common symptoms of sepiapterin reductase deficiency occurring in the first to tenth month of life include delayed development, periodic fixed upward or sideways gazing of the eyes (oculogyric crisis), and reduced muscle tone (hypotonia) which may progress to hyper- or extra-toned muscles (hypertonia). Infants with this deficiency may also show other signs of nerve impairment such as muscle weakness.[1]

Some infants and children with sepiapterin reductase deficiency develop dystonia. Dystonia refers to unusual body posturing or twisting movements that are caused by uncontrolled muscle contractions. Muscle control may be better during certain periods of the day (such as in the morning). In addition, some children with this deficiency developed tremors, excessive sweating, and excessive sleepiness. Less frequent symptoms include drooling, difficulty speaking words clearly, abnormal tongue movements, abnormal gait (walk), occasional seizure, delayed growth, small head size, and Gower’s sign (which shows weakness of proximal muscles, particularly of the hip and thigh muscles).
Last updated: 2/18/2009

What is autosomal recessive inheritance?

Autosomal recessive inheritance refers to the inheritance pattern in which two mutated copies of the gene that causes a disorder are present in each cell. An affected person usually has unaffected parents who each carry a single copy of the mutated gene (and are referred to as carriers). Autosomal recessive disorders are typically not seen in every generation of an affected family. When two people who are carriers of an autosomal recessive condition have a child, there is a 25% (1 in 4) chance that the child will be affected.[3]
Last updated: 2/18/2009

How is sepiapterin reductase deficiency diagnosed?

Sepiapterin reductase deficiency may be considered in children with early-onset encephalopathy with motor delays, particularly in children with periodic locked upward or sideways eye gaze (oculogyric crisis), abnormal body movements, and posturing. Diagnosis is based on careful examination of neurotransmitters in the cerebrospinal fluid. People with sepiapterin reductase deficiency show abnormalities in the metabolic pathway of dopamine, serotonin, biopterin, and their metabolites. Further testing of cerebrospinal fluid for sepipterin may be necessary. Testing for dihydropteridin reductase and sepiapterin reductase in fibroblasts may also be recommended.[1]
Last updated: 2/18/2009

How might sepiapterin reductase deficiency be treated?

Treatment of sepiapterin reductase deficiency may involve levodopa, carbidopa and 5-hydroxytryptophan. General information on levodopa and carbidopa can be found on the MedlinePlus Web site by clicking here.  

The amounts of levodopa and carbidopa administered to people with sepiapterin reductase deficiency vary, but, in general, tends to be between 1 and 10 mg/kg/day in three or four doses. 5-hydroxytryptophan doses tend to be between 1 to 8 mg/kg/day also in three or four doses. This combination therapy is introduced slowly and increased by 1 mg/kg or less over days or weeks until the final target concentration is reached. Folinic acid supplementation may also be needed. Therapy with levodopa and carbidopa alone or in combination with tetrahydrobiopterin may be considered for people who do not respond well to 5-hydroxytryptophan.[1]

People receiving the levodopa treatment regimen require careful monitoring because increasing the dose too quickly can cause side-effects. Patients recieving treatment may be monitored with routine evaluations by a pediatric neurologist, video documentation, and follow-up testing looking at cerebral spinal fluid (CSF) metabolite concentrations. Samples of CSF are obtained by lumbar puncture. In addition, monitoring prolactin levels may be informative for patients who had high levels of prolactin before starting levodopa therapy.[1]
Last updated: 2/18/2009

Does it take a while for levodopa medications to become effective?

Not typically. Levodopa therapy may result in noticeable improvements (particularly in motor skills) days and in some cases hours following treatment.[1]
Last updated: 2/18/2009

What is the typical prognosis for people with sepiapterin reductase deficiency?

Children with sepiapterin reductase deficiency treated with levodopa medications tend to show great improvement in motor skills. Previously wheelchair-bound children have become able to walk, run, and play sports with levodopa therapy. The effectiveness of levodopa therapy on improvement of learning abilities vary. Children often have moderate-to-significant learning disabilities despite therapy.[1]
Last updated: 2/18/2009

Are there any clinical trials enrolling people with sepiapterin reductase deficiency?

The National Institutes of Health, through the National Library of Medicine, developed to provide patients, family members, and members of the public with current information on clinical research studies. While no studies involving sepiapterin reductase deficiency specifically are listed at this time there is a study, entitled "Studies of Children with Metabolic and Other Genetic Diseases", which is evaluating individuals with known or suspected genetic or metabolic diseases. Despite its title, this study is enrolling individuals of all ages. To read about this study, click on the link below. After you click on the study, review its 'eligibility' criteria to determine its appropriateness.
You can also contact the Patient Recruitment and Public Liaison (PRPL) Office at the National Institutes of Health (NIH). We recommend calling the toll-free number listed below to speak with a specialist, who can help you determine if your daughter is eligible for any clinical trials.

Patient Recruitment and Public Liaison Office (PRPL)
NIH Clinical Center
Bethesda, Maryland 20892-2655
Toll-free: 800-411-1222
Fax: 301-480-9793
Web site:  

You can find helpful general information on clinical trials at the following Web page.  

A tutorial about clinical trials that can also help answer your questions can be found at the following link from the National Library of Medicine.

Resources on many charitable or special-fare flights to research and treatment sites and low-cost hospitality accommodations for outpatients and family members, as well as ambulance services, are listed on the Web site of the Office of Rare Diseases (ORD), part of the National Institutes of Health.  
Last updated: 2/18/2009

Other Names for this Disease
  • SPR deficiency
Related Diseases
See Disclaimer regarding information on this site. Some links on this page may take you to organizations outside of the National Institutes of Health.