Pathways

Sepiapterin reductase deficiency results from a metabolic disorder; namely, the underproduction of Sepiapterin. The cause of this underproduction is an autosomal recessive genetic mutation in the SPR gene. This gene is responsible for Sepiapterin production, and naturally, when the gene malfunctions the production of this metabolite is altered leading to a range of effects on the body. In this case, some symptoms of Sepiapterin Deficiency are: motor and speech delay, axial hypotonia, dystonia, weakenss microcephaly, dysarthria, autonomic dysfunction, oculogyric crises, drowsiness, among others.

Sepiapterin reductase deficiency results from a metabolic disorder; namely, the underproduction of Sepiapterin. The cause of this underproduction is an autosomal recessive genetic mutation in the SPR gene. This gene is responsible for Sepiapterin production, and naturally, when the gene malfunctions the production of this metabolite is altered leading to a range of effects on the body. In this case, some symptoms of Sepiapterin Deficiency are: motor and speech delay, axial hypotonia, dystonia, weakenss microcephaly, dysarthria, autonomic dysfunction, oculogyric crises, drowsiness, among others.

Sepiapterin reductase deficiency results from a metabolic disorder; namely, the underproduction of Sepiapterin. The cause of this underproduction is an autosomal recessive genetic mutation in the SPR gene. This gene is responsible for Sepiapterin production, and naturally, when the gene malfunctions the production of this metabolite is altered leading to a range of effects on the body. In this case, some symptoms of Sepiapterin Deficiency are: motor and speech delay, axial hypotonia, dystonia, weakenss microcephaly, dysarthria, autonomic dysfunction, oculogyric crises, drowsiness, among others.

Sepiapterin reductase deficiency is a genetic disorder that is characterized by abnormal levels of neurotransmitters and pterins. It is caused an autosomal recessive genetic mutation in the SPR gene which leads to the underproduction of the enzyme sepiapterin reductase. Sepiapterin reductase is an enzyme required in multiple steps of the synthesis of tetrahydrobiopterin which is needed in the synthesis of the neurotransmitters dopamine and serotonin. The deficiency of sepiapterin reductase also causes an accumulation of sepiapterin. Symptoms of sepiapterin reductase deficiency include Motor and speech delay, axial hypotonia, dystonia, weakenss microcephaly, dysarthria, autonomic dysfunction, oculogyric crises, and drowsiness. Parkinsonian signs (tremor, bradykinesia, masked facies, rigidity), limb hypertonia, hyperreflexia, intellectual disability, psychiatric and/or behavioral abnormalities, autonomic dysfunction, and sleep disturbances are also common features of Sepiapterin reductase deficiency.

Serdexmethylphenidate, known commonly combined with dexmethylphenidate as Azstarys, is a prodrug of dexmethylphenidate (CNS stimulant) used for first-line treatment of ADHD. ADHD is caused by an abnormality in the dopamine transporter gene (DAT1), the D4 receptor gene (DRD-4), and/or the D2 receptor gene. It has also been found to affect the alpha-2A adrenergic receptor in the prefrontal cortex. This abnormality makes it harder for dopamine and norepinephrine to bind to the receptors. These receptors regulate attention, movement, and impulsivity, so a deficiency in the regulation of those systems causes ADHD. Serdexmethylphenidate blocks the reuptake transporters of dopamine and norepinephrine, prolonging their duration in the synapse so that they can bind more readily to the receptors. Since it works in the brain, Serdexmethylphenidate crosses the blood-brain barrier through diffusion. Dopamine is synthesized in the ventral tegmental area of the brain from tyrosine being synthesized into L-dopa by the enzyme Tyrosine 3-monooxygenase . L-Dopa is then synthesized into dopamine with the enzyme aromatic-L-amino-acid decarboxylase. Dopamine then travels to the prefrontal cortex, which is released into the synapse when the neuron is stimulated and fires. Serdexmethylphenidate binds to the sodium-dependent dopamine transporter, preventing dopamine from re-entering the presynaptic neuron. The dopamine then binds to Dopamine D4 receptors on the postsynaptic membrane. The dopamine D4 receptor activates the Gi protein cascade, which inhibits adenylate cyclase. This prevents adenylate cyclase from catalyzing ATP into cAMP. The low concentration of cAMP is unable to activate protein kinase A, which prevents or lowers neuronal excitability. It is unknown how exactly this helps with ADHD, but it is speculated to help by regulating attention, movement, and impulsivity to a greater degree. Other dopamine and norepinephrine receptors are likely also involved, but the main receptors complicit in ADHD are the dopamine D4 receptor and the alpha-2A adrenergic receptor. This helps people with ADHD to sustain attention and working memory.