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Genetics Home Reference: your guide to understanding genetic conditions
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Sepiapterin reductase deficiency

Reviewed June 2011

What is sepiapterin reductase deficiency?

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.

People with sepiapterin reductase deficiency may have additional signs and symptoms including an unusually small head size (microcephaly), intellectual disability, seizures, excessive sleeping, and mood swings.

How common is sepiapterin reductase deficiency?

Sepiapterin reductase deficiency appears to be a rare condition. At least 30 cases have been described in the scientific literature.

What genes are related to sepiapterin reductase deficiency?

Mutations in the SPR gene cause sepiapterin reductase deficiency. The SPR gene provides instructions for making the sepiapterin reductase enzyme. This enzyme is involved in the production of a molecule called tetrahydrobiopterin (also known as BH4). Specifically, sepiapterin reductase is responsible for the last step in the production of tetrahydrobiopterin. Tetrahydrobiopterin helps process several building blocks of proteins (amino acids), and is involved in the production of chemicals called neurotransmitters, which transmit signals between nerve cells in the brain.

SPR gene mutations disrupt the production of sepiapterin reductase. Most SPR gene mutations result in an enzyme with little or no function. A nonfunctional sepiapterin reductase leads to a lack of tetrahydrobiopterin. In most parts of the body, there are alternate pathways that do not use sepiapterin reductase for the production of tetrahydrobiopterin, but these pathways are not found in the brain. Therefore, people with sepiapterin reductase deficiency have a lack of tetrahydrobiopterin in the brain. When no tetrahydrobiopterin is produced in the brain, production of dopamine and serotonin is greatly reduced. Among their many functions, dopamine transmits signals within the brain to produce smooth physical movements, and serotonin regulates mood, emotion, sleep, and appetite. The lack of these two neurotransmitters causes the problems with movement and other features of sepiapterin reductase deficiency.

Related Gene(s)

Changes in this gene are associated with sepiapterin reductase deficiency.

  • SPR

How do people inherit sepiapterin reductase deficiency?

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Where can I find information about diagnosis or management of sepiapterin reductase deficiency?

These resources address the diagnosis or management of sepiapterin reductase deficiency and may include treatment providers.

  • Genetic Testing Registry: Sepiapterin reductase deficiency (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0268468)

You might also find information on the diagnosis or management of sepiapterin reductase deficiency in Educational resources (http://www.ghr.nlm.nih.gov/condition/sepiapterin-reductase-deficiency/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/sepiapterin-reductase-deficiency/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about sepiapterin reductase deficiency?

You may find the following resources about sepiapterin reductase deficiency helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for sepiapterin reductase deficiency?

  • dopa-responsive dystonia due to sepiapterin reductase deficiency
  • SPR deficiency

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about sepiapterin reductase deficiency?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding sepiapterin reductase deficiency?

acids ; ataxia ; autosomal ; autosomal recessive ; cell ; chorea ; deficiency ; disability ; dopamine ; dystonia ; enzyme ; gene ; inherited ; involuntary ; microcephaly ; molecule ; motor ; neurotransmitters ; phenylalanine ; recessive ; spasticity

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Abeling NG, Duran M, Bakker HD, Stroomer L, Thöny B, Blau N, Booij J, Poll-The BT. Sepiapterin reductase deficiency an autosomal recessive DOPA-responsive dystonia. Mol Genet Metab. 2006 Sep-Oct;89(1-2):116-20. Epub 2006 May 2. (http://www.ncbi.nlm.nih.gov/pubmed/16650784?dopt=Abstract)
  • Arrabal L, Teresa L, Sánchez-Alcudia R, Castro M, Medrano C, Gutiérrez-Solana L, Roldán S, Ormazábal A, Pérez-Cerdá C, Merinero B, Pérez B, Artuch R, Ugarte M, Desviat LR. Genotype-phenotype correlations in sepiapterin reductase deficiency. A splicing defect accounts for a new phenotypic variant. Neurogenetics. 2011 Aug;12(3):183-91. doi: 10.1007/s10048-011-0279-4. Epub 2011 Mar 24. (http://www.ncbi.nlm.nih.gov/pubmed/21431957?dopt=Abstract)
  • Blau N, Bonafé L, Thöny B. Tetrahydrobiopterin deficiencies without hyperphenylalaninemia: diagnosis and genetics of dopa-responsive dystonia and sepiapterin reductase deficiency. Mol Genet Metab. 2001 Sep-Oct;74(1-2):172-85. Review. (http://www.ncbi.nlm.nih.gov/pubmed/11592814?dopt=Abstract)
  • Echenne B, Roubertie A, Assmann B, Lutz T, Penzien JM, Thöny B, Blau N, Hoffmann GF. Sepiapterin reductase deficiency: clinical presentation and evaluation of long-term therapy. Pediatr Neurol. 2006 Nov;35(5):308-13. (http://www.ncbi.nlm.nih.gov/pubmed/17074599?dopt=Abstract)
  • Longo N. Disorders of biopterin metabolism. J Inherit Metab Dis. 2009 Jun;32(3):333-42. doi: 10.1007/s10545-009-1067-2. Epub 2009 Feb 9. Review. Erratum in: J Inherit Metab Dis. 2009 Jun;32(3):457. (http://www.ncbi.nlm.nih.gov/pubmed/19234759?dopt=Abstract)
  • Neville BG, Parascandalo R, Farrugia R, Felice A. Sepiapterin reductase deficiency: a congenital dopa-responsive motor and cognitive disorder. Brain. 2005 Oct;128(Pt 10):2291-6. Epub 2005 Jul 27. (http://www.ncbi.nlm.nih.gov/pubmed/16049044?dopt=Abstract)
  • Verbeek MM, Willemsen MA, Wevers RA, Lagerwerf AJ, Abeling NG, Blau N, Thöny B, Vargiami E, Zafeiriou DI. Two Greek siblings with sepiapterin reductase deficiency. Mol Genet Metab. 2008 Aug;94(4):403-9. doi: 10.1016/j.ymgme.2008.04.003. Epub 2008 May 27. (http://www.ncbi.nlm.nih.gov/pubmed/18502672?dopt=Abstract)
  • Zorzi G, Redweik U, Trippe H, Penzien JM, Thöny B, Blau N. Detection of sepiapterin in CSF of patients with sepiapterin reductase deficiency. Mol Genet Metab. 2002 Feb;75(2):174-7. (http://www.ncbi.nlm.nih.gov/pubmed/11855937?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: June 2011
Published: September 29, 2014