What is Sepiapterin Reductase Deficiency?

Sepiapterin reductase (SPR) deficiency is a type of neurotransmitter disorder. Like other neurotransmitter disorders it can also be classified as a rare inborn error of metabolism. SPR deficiency disrupts the production of the enzyme sepiapterin reductase which is involved in the production of a molecule call tetrahydrobiopterin (also known as BH4) in the brain.

Tetrahydrobiopterin helps process several building blocks of proteins (amino acids), and is involved in the production of the neurotransmitter dopamine and serotonin.

When no tetrahydrobiopterin is produced in the brain the production of dopamine and serotonin is greatly reduced. The lack of neurotransmitters causes problems with movement and other symptoms associated with neurotransmitter deficits.

What symptoms are associated with SPR Deficiency? SPR deficiency often occurs in the first ten months of life.

Common symptoms:

• Delayed development
• Periodic fixed upward or sideways gazing of the eyes (oculogyric crisis)
• Reduced muscle tone (hypotonia)
• Unusual body posturing/twisting movements (dystonia)
• Tremors
• Muscle control better at different times of day (diurnal effects)

Additional symptoms:

• Tremors
• Excessive sweating
• Excessive sleepiness

Severe symptoms:

• Drooling
• Difficulty speaking
• Abnormal tongue movements
• Occasional seizure
• Delayed growth
• Small head size
• Weakness of hip and thigh muscles (Gowers sign)

What causes SPR Deficiency?

SPR Deficiency is caused by mutations in the SPR gene. The SPR gene provides instructions for making the enzyme sepiapterin reductase. Specifically, sepiapterin reductase is responsible for the last step in the production of tetrahydrobiopterin. Most SPR gene mutations result in an enzyme with little or no function.

A nonfunctional sepiapterin reductase gene leads to a lack of tetrahydrobiopterin which causes a disruption in neurotransmitter metabolism. SPR Deficiency is due to an autosomal recessive inheritance.

In this type of inheritance pattern there are two mutated copies of the gene that causes the disorder. A person with SPR deficiency usually has unaffected parents (no symptoms) 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. For additional information on genetic diseases click the disease link then genetic disease link.

Who gets SPR Deficiency?

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

How is SPR Deficiency Diagnosed?

Diagnosis is based on specific and careful examination of neurotransmitter metabolites in the cerebrospinal fluid (CSF) via lumbar puncture. CSF testing for SPR Deficiency shows abnormalities in the metabolic pathway of dopamine, serotonin, biopterin and their metabolites.

Further testing of the CSF for sepipterin may be necessary. Testing for SPR deficiency in fibroblasts (cells that can be used for genetic testing) may also be recommended.

For additional information click testing on the home page.