Sepiapterin reductase deficiency (SRD) is a rare genetic disorder primarily characterized by movement problems, most notably dystonia, a condition causing involuntary and sustained muscle contractions.
Understanding Sepiapterin Reductase Deficiency
SRD affects the body's ability to produce tetrahydrobiopterin (BH4), an essential enzyme cofactor crucial for various biochemical processes. BH4 is vital for the synthesis of several neurotransmitters, including dopamine, serotonin, norepinephrine, and nitric oxide. The deficiency disrupts these pathways, leading to a range of neurological symptoms.
Key Features of SRD
- Dystonia: The hallmark of SRD is dystonia, often manifesting as involuntary muscle contractions that lead to repetitive movements or abnormal postures.
- Developmental Delays: Infants and children with SRD may exhibit delays in reaching developmental milestones, such as sitting, crawling, or walking.
- Hypotonia: Some individuals may experience hypotonia, or low muscle tone, particularly in early infancy.
- Seizures: Seizures can occur in some cases of SRD.
- Psychiatric Symptoms: Behavioral or psychiatric issues, such as irritability, anxiety, or depression, may be present.
- Oculogyric Crises: Involuntary upward movements of the eyes can sometimes occur.
Diagnosis and Treatment
Diagnosis typically involves biochemical testing to measure BH4 levels and enzyme activity, along with genetic testing to identify mutations in the SPR gene, which encodes sepiapterin reductase. Treatment focuses on managing symptoms and providing neurotransmitter supplementation, often with L-dopa and 5-hydroxytryptophan, to address the dopamine and serotonin deficiencies. Early diagnosis and intervention are crucial to improving outcomes for individuals with SRD.
Genetic Basis
SRD is an autosomal recessive disorder, meaning that an affected individual must inherit two copies of the mutated SPR gene—one from each parent.
