The enzyme is involved in the last step of producing tetrahydrobiopterin, better known as BH4. BH4 is involved in the processing of amino acids and the production of neurotransmitters, specifically that of dopamine and serotonin which are primarily used in transmission of signals between nerve cells in the brain. The mutation in the SPR gene interferes with the production of the enzyme by producing enzymes with little or no function at all. This interference results in a lack of BH4 specifically in the brain. The lack of BH4 only occurs in the brain because other parts of the body adapt and utilize alternate pathways for the production of BH4. The mutation in the SPR gene leads to nonfunctional sepiapterin reductase enzymes, which results in a lack of BH4 and ultimately disrupts the production of dopamine and serotonin in the brain. The disruption of dopamine and serotonin production leads to the visible symptoms present in patients suffering from sepiapterin reductase deficiency. SR deficiency is considered an inherited autosomal recessive condition disorder because each parent carries one copy of the mutated gene, but typically do not show any signs or symptoms of the condition. Diagnosis
CSF neurotransmitter screening
The diagnosis of SR deficiency is based on the analysis of the pterins and biogenic amines found in the cerebrospinal fluid (CSF) of the brain. The pterin compound functions as a cofactor in enzyme catalysis and biogenic amines which include adrenaline, dopamine, and serotonin have functions that vary from the control of homeostasis to the management of cognitive tasks.
Quantification of Sepiapterin in CSF
This study examined the clinical history of the CSF and urine of two Greek siblings who were both diagnosed with SR deficiency. Both siblings displayed delayed psychomotor development and a movement disorder. The diagnosis was confirmed by measuring the SR enzyme activity and mutation analysis. The mutation analysis of the gene was performed using genomic DNA isolated from blood samples. The results concluded that both patients have low concentrations of HVA and HIAA and high concentrations of sepiapterin in the CSF, but neopterin and biopterin were abnormal in only one sibling. The results of this research indicates that when diagnosing the SR deficiency, the quantification of sepiapterin in the CSF is more important and indicative of SR deficiency than using neopterin and biopterin alone. The results also show that the urine concentrations of neurotransmitter metabolites are abnormal in patients with this disorder. This finding may provide an initial and easier indication of the deficiency before CSF analysis is performed. Figures
See also
Succinic semialdehyde dehydrogenase deficiency
Neurotransmitter
Parkinsons disease
Cerebral palsy
Enzyme
Biochemistry

References
External links
SR deficiency Genetics Home Reference
SR deficiency National Institute of Health