Sepiapterin reductase deficiency (sepiapterin reductase deficiency) - Gen SPR.  

Sepiapterin reductase deficiency is a disorder characterized by movement problems, such as dystonia, spasticity, tremors, ataxia and chorea. In addition, people with sepiapterin reductase deficiency may have oculogyration. These episodes involving abnormal rotation of the eyes, irritability, extreme agitation, pain, muscle spasms, and uncontrolled movements, especially of the head and neck. Often these abnormal movements are more intense at the end of the day. The most affected people have delayed development of motor skills and, generally, are not able to walk unassisted. Problems with movement tend to worsen over time. Other signs and symptoms may include additional microcephaly, mental retardation, seizures, excessive sleepiness and mood swings.

This process is due to mutations in SPR gene located on the short arm of chromosome 2 (2p14-p12). This gene encodes sepiapterin reductase. This enzyme is involved in the production of tetrahydrobiopterin (also known as BH4). Specifically, sepiapterin reductase is responsible for the final step in the production of tetrahydrobiopterin. Tetrahydrobiopterin normally helps process several amino acids, including phenylalanine. It is also involved in the production of neurotransmitters. Specifically, tetrahydrobiopterin is involved in the production of dopamine and serotonin. Among its many functions, the dopamine transmits signals within the brain to produce smooth physical movement, while serotonin regulates mood, emotion, sleep and appetite.

They have identified more than a dozen in the SPR gene mutations leading to deficiency sepiapterin reductase. These mutations disrupt the coding sepiapterin reductase. Most mutations lead to an enzyme with little or no function, which causes a deficiency of tetrahydrobiopterin. A common mutation in affected individuals replaces the amino acid arginine by the amino acid glycine at position 150 in the enzyme (Arg150Gly or R150G), thereby inhibiting any coding sepiapterin reductase. In most parts of the body, there are alternative paths that do not use sepiapterin reductase to produce tetrahydrobiopterin, but these roads are not in the brain. Therefore, people with sepiapterin reductase deficiency have a lack of tetrahydrobiopterin in the brain. When no tetrahydrobiopterin occurs in the brain, the production of dopamine and serotonin is reduced considerably. The lack of these two neurotransmitters causes problems with movement and other characteristics of sepiapterin reductase deficiency.

This disease is inherited in an autosomal recessive pattern, that is, both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.

Tests in IVAMI: in IVAMI perform detection of mutations associated with sepiapterin reductase deficiency, by complete PCR amplification of the exons of SPR gene and subsequent sequencing.