Summary about Disease
Sepiapterin reductase deficiency (SRD) is a rare genetic disorder affecting the production of tetrahydrobiopterin (BH4). BH4 is an essential cofactor for several enzymes involved in the synthesis of neurotransmitters like dopamine, serotonin, and norepinephrine, as well as nitric oxide. SRD leads to neurological problems, movement disorders, and developmental delays due to the deficiency of these crucial substances. It's a treatable form of phenylketonuria (PKU) with unique characteristics.
Symptoms
Symptoms can vary in severity but commonly include:
Hypotonia (floppy muscle tone)
Movement disorders (dystonia, tremors, rigidity)
Developmental delay
Seizures
Intellectual disability
Irritability
Drowsiness
Swallowing difficulties
Drooling
Oculogyric crises (involuntary upward movement of the eyes)
Sensitivity to heat
Behavioral problems
Causes
SRD is caused by mutations in the SPR gene. This gene provides instructions for making the sepiapterin reductase enzyme. Mutations in the *SPR* gene lead to a deficiency of the functional enzyme, resulting in reduced BH4 production. It is inherited in an autosomal recessive pattern, meaning both parents must carry a copy of the mutated gene for their child to be affected.
Medicine Used
Treatment aims to replenish the deficient neurotransmitters:
L-Dopa/Carbidopa: To increase dopamine levels. Carbidopa helps prevent L-Dopa from being converted to dopamine before it reaches the brain.
5-Hydroxytryptophan (5-HTP): A precursor to serotonin.
Folinic acid (Leucovorin): Helps to improve neurological function.
BH4 (Kuvan): May be effective in some cases, depending on the specific mutation and the level of enzyme deficiency.
Is Communicable
No, sepiapterin reductase deficiency is not communicable. It is a genetic disorder caused by a gene mutation and cannot be spread from person to person.
Precautions
Genetic counseling is recommended for families with a history of SRD to understand the risk of recurrence in future pregnancies.
Strict adherence to the prescribed medication regimen is crucial for managing symptoms and preventing complications.
Regular monitoring by a metabolic specialist or neurologist is essential to adjust treatment as needed.
Avoidance of high temperatures and dehydration is advisable due to sensitivity to heat.
How long does an outbreak last?
SRD is not an "outbreak"-related disease. It's a chronic, lifelong condition. Symptoms can fluctuate in severity depending on the effectiveness of treatment and other factors like illness or stress.
How is it diagnosed?
Diagnosis typically involves:
Newborn screening: Elevated phenylalanine levels, similar to PKU, may raise suspicion.
Urine pterin analysis: Elevated sepiapterin and decreased biopterin levels in urine are characteristic.
Red blood cell dihydropteridine reductase (DHPR) activity: This enzyme is usually normal in SRD, which helps differentiate it from other BH4 deficiencies.
Genetic testing: Sequencing of the SPR gene to identify mutations.
Neurotransmitter metabolite analysis: Measuring dopamine and serotonin metabolites in cerebrospinal fluid (CSF) can provide additional diagnostic information.
Timeline of Symptoms
Symptoms can appear at various ages, often starting in infancy or early childhood. The timeline can vary widely:
Infancy: Hypotonia, feeding difficulties, drowsiness, seizures may be the first signs.
Early Childhood: Developmental delay, movement disorders (dystonia, tremors), behavioral problems become more apparent.
Later Childhood/Adolescence: If untreated or poorly managed, intellectual disability and progressive neurological problems may develop.
The severity of symptoms and the age of onset depend on the specific genetic mutation and the degree of enzyme deficiency.
Important Considerations
Early diagnosis and treatment are crucial to minimize neurological damage and improve long-term outcomes.
SRD can mimic cerebral palsy due to the presence of movement disorders, so accurate diagnosis is critical.
Treatment is usually lifelong, and dosage adjustments may be necessary as the child grows.
A multidisciplinary team, including a metabolic specialist, neurologist, developmental pediatrician, and genetic counselor, is essential for comprehensive care.
Research is ongoing to better understand the disease and develop new therapies.