Introduction
Dihydropteridine reductase deficiency (DHPRD) is a rare genetic disorder that affects the body's ability to produce certain neurotransmitters, including dopamine, norepinephrine, and serotonin.
DHPRD typically appears in infancy or early childhood and can include developmental delays, seizures, tremors, hyperactivity, and behavioral problems.
What Is the Role of Dihydropteridine Reductase in the Body?
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Dihydropteridine reductase is an enzyme that plays a critical role in synthesizing neurotransmitters in the body.
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It converts a precursor molecule called dihydrobiopterin (BH2) into tetrahydrobiopterin (BH4), an essential cofactor for producing neurotransmitters including dopamine, norepinephrine, and serotonin.
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DHPR is crucial for proper brain function and regulates mood, behavior, and movement.
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DHPR is found primarily in the liver and the brain, where it plays a critical role in maintaining normal levels of neurotransmitters.
What Are the Causes of Dihydropteridine Reductase Deficiency?
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Dihydropteridine reductase (DHPR) deficiency is a rare autosomal recessive disorder (meaning that affected individuals inherit two copies of the mutated gene, one from each parent).
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It is caused by mutations in the QDPR gene, which provides instructions for making the enzyme dihydropteridine reductase (DHPR)
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DHPR plays a critical role in the production of tetrahydrobiopterin (BH4), which is a cofactor for several enzymes involved in the synthesis of neurotransmitters such as dopamine, serotonin, and norepinephrine.
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When DHPR activity is reduced or absent, BH4 production is impaired, leading to decreased neurotransmitter synthesis and subsequent neurological symptoms.
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It affects the metabolism of phenylalanine, an amino acid found in many foods.
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Phenylalanine is normally converted into tyrosine through a process that requires the enzyme dihydropteridine reductase (DHPR).
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Due to a lack of this enzyme in people with DHPRD, phenylalanine builds up and the production of neurotransmitters such as dopamine, serotonin, and norepinephrine is reduced.
What Are the Symptoms of Dihydropteridine Reductase Deficiency?
Dihydropteridine reductase deficiency (DHPRD) symptoms can range considerably but frequently include the following:
1. Developmental Delay:
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Children with DHPRD frequently experience developmental delays. It refers to a significant delay or impairment in the acquisition of developmental milestones that are expected for a child's age.
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In DHPRD, developmental delay can affect motor skills such as crawling and walking, as well as speech and language skills.
2. Seizures:
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Affected individuals can have different levels of severity and frequency of seizures.
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Seizures can be localized or generalized, and they might manifest as subtle staring spells, brief muscle contractions, or convulsions involving the entire body.
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The onset of seizures can occur in infancy or early childhood and may be the first sign of the disorder.
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Seizures may be difficult to control with antiepileptic medications in some individuals.
3. Tremors:
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Tremors are a common symptom of DHPRD.
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They refer to involuntary shaking or trembling of the body or limbs.
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The tremors can be mild or severe and can affect the hands, legs, or other parts of the body.
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The severity and frequency of tremors may vary among individuals with DHPRD. Some individuals may experience tremors only during certain activities or times of the day, while others may have constant tremors.
4. Hyperactivity:
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Hyperactivity is a symptom commonly seen in children with DHPRD.
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They may exhibit restless behavior, have difficulty remaining still or sitting in one place, and struggle with paying attention to tasks or activities.
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This can lead to academic and social difficulties in school and at home.
5. Behavioral Problems:
DHPRD can affect behavior and social interactions in affected individuals, leading to a range of behavioral problems. Some common examples include:
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Aggression: Some individuals with DHPRD may exhibit aggressive behavior, such as hitting, biting, or kicking others. This behavior may be due to frustration or an inability to communicate effectively.
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Impulsivity: DHPRD may cause impulsivity, which is characterized by acting without thinking about the consequences. Impulsive actions like dashing into traffic or jumping from tall objects may arise from this.
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Difficulty With Social Interaction: Children with DHPRD may have difficulty with social interactions, such as making friends or understanding social cues. They may also struggle with emotional regulation and may have outbursts of emotion in inappropriate situations.
6. Dystonia:
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In some cases, affected individuals may also experience a progressive movement disorder called dystonia.
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Dystonia is a neurological condition characterized by involuntary muscle contractions that cause abnormal postures and repetitive movements.
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Dystonia can worsen with time and affect several body areas, including the limbs, face, neck, and trunk.
These symptoms are related to the reduced levels of neurotransmitters in the brain, which can impair brain function and lead to cognitive and behavioral problems.
How to Diagnose Dihydropteridine Reductase Deficiency?
The diagnosis of DHPRD is usually made through a combination of clinical findings, biochemical testing, and genetic testing.
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Clinical Findings: It may include developmental delay, seizures, tremors, hyperactivity, behavioral problems, and/or a progressive movement disorder called dystonia.
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Biochemical Testing: Measurements of phenylalanine, tyrosine, and neurotransmitter metabolites in the blood and cerebrospinal fluid (CSF) are routine components of biochemical testing. DHPRD is usually characterized by high levels of phenylalanine and low levels of tyrosine and neurotransmitter metabolites in the blood and CSF.
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Genetic Testing: The genetic mutation that is causing the illness can be found utilizing genetic testing, which can also confirm the diagnosis. Genetic testing is usually done by sequencing the DHPR gene located on chromosome 12q22-qter, which is responsible for encoding the enzyme dihydropteridine reductase.
How to Treat Dihydropteridine Reductase Deficiency?
The treatment for DHPRD typically involves a combination of medications and dietary modifications to manage the symptoms of the disease.
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One of the main treatments for DHPRD is the use of supplements such as L-dopa, which can help increase dopamine levels in the brain.
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Other supplements, such as 5-hydroxytryptophan (5-HTP), may also be used to increase levels of serotonin, a neurotransmitter that helps regulate mood and behavior.
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In addition to medication, individuals with DHPRD may benefit from a low-protein diet to help reduce the buildup of toxic byproducts in the body.
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They may also benefit from physical therapy and occupational therapy to improve motor skills and promote independent living.
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Treatment for DHPRD is typically lifelong, and regular monitoring by a healthcare team is necessary to adjust medication and diet as needed and manage any potential complications of the disease.
Conclusion
Dihydropteridine reductase deficiency (DHPRD) is a rare genetic disorder that affects the production of neurotransmitters in the brain, leading to various neurological symptoms. These symptoms may include developmental delay, seizures, tremors, hyperactivity, and behavioral problems. In some cases, individuals with DHPRD may also develop a progressive movement disorder called dystonia.
There is currently no cure for DHPRD, and treatment options focus on managing symptoms. This may include medications to increase neurotransmitter levels in the brain and therapies such as occupational therapy and speech therapy. Early diagnosis and treatment may help improve outcomes for individuals with DHPRD.
Despite the fact that DHPRD is a rare condition, it can have a profound impact on those who are affected and their family. Support from the community and medical experts can be helpful in managing the condition and raising the quality of life.
