Summary about Disease
Dihydrobiopterin reductase deficiency (DHPR deficiency) is a rare genetic disorder that disrupts the body's ability to process tetrahydrobiopterin (BH4). BH4 is an essential cofactor involved in several important metabolic pathways, including the production of neurotransmitters like dopamine, norepinephrine, and serotonin, as well as the breakdown of phenylalanine (an amino acid). Deficiency of DHPR leads to atypical phenylketonuria (PKU) and a shortage of neurotransmitters, impacting neurological function and development.
Symptoms
Symptoms of DHPR deficiency can vary in severity and may include:
Developmental delays
Intellectual disability
Seizures
Movement disorders (e.g., hypotonia, rigidity, dystonia)
Microcephaly (small head size)
Irritability
Difficulty feeding
Swallowing problems
Hypersalivation
Sleep disturbances
Progressive neurological deterioration
Causes
DHPR deficiency is caused by mutations in the QDPR gene. This gene provides instructions for making the dihydrobiopterin reductase enzyme. Mutations in the *QDPR* gene lead to a non-functional or deficient enzyme, which impairs BH4 recycling. It is inherited in an autosomal recessive pattern, meaning that both parents must carry a copy of the mutated gene for a child to be affected.
Medicine Used
Treatment focuses on replacing the deficient neurotransmitters and managing phenylalanine levels. Medications may include:
Sapropterin dihydrochloride: A synthetic form of BH4 that can help improve enzyme function in some cases.
L-Dopa and carbidopa: To increase dopamine levels.
5-Hydroxytryptophan (5-HTP): To increase serotonin levels.
Folinic acid: May be required to counteract neurological symptoms.
Phenylalanine-restricted diet: To control phenylalanine levels, similar to the treatment for PKU.
Is Communicable
No, DHPR deficiency is not communicable. It is a genetic disorder caused by gene mutations and cannot be transmitted from person to person through any infectious means.
Precautions
Precautions mainly involve adherence to the prescribed treatment plan, including:
Strict adherence to the phenylalanine-restricted diet.
Careful monitoring of blood phenylalanine levels.
Regular neurological evaluations and developmental assessments.
Prompt treatment of seizures or other neurological symptoms.
Consistent administration of prescribed medications.
Genetic counseling for families affected by DHPR deficiency.
How long does an outbreak last?
DHPR deficiency is not an infectious disease and does not involve outbreaks. It is a chronic, lifelong condition requiring ongoing management.
How is it diagnosed?
Diagnosis typically involves:
Newborn screening: Elevated phenylalanine levels detected during routine newborn screening may suggest PKU. Follow-up testing is necessary to differentiate DHPR deficiency from classical PKU.
Blood and urine tests: Measurement of biopterin and neopterin levels in blood and urine can help identify BH4 deficiencies.
DHPR enzyme assay: Measurement of DHPR enzyme activity in red blood cells.
Genetic testing: Analysis of the QDPR gene to identify mutations.
Neurotransmitter analysis: Analysis of cerebrospinal fluid (CSF) to measure neurotransmitter levels.
Timeline of Symptoms
The timeline of symptoms can vary, but generally:
Early infancy: Elevated phenylalanine levels are detected in newborn screening. Symptoms may begin to appear within the first few months of life.
Infancy/early childhood: Developmental delays, seizures, movement disorders, and feeding difficulties become apparent.
Childhood/adolescence: If untreated or poorly managed, neurological deterioration, intellectual disability, and behavioral problems may worsen.
Important Considerations
Early diagnosis and treatment are crucial for preventing or minimizing neurological damage.
Treatment requires a multidisciplinary approach involving metabolic specialists, neurologists, dietitians, and other healthcare professionals.
Long-term monitoring and management are essential.
Genetic counseling is recommended for families to understand the inheritance pattern and recurrence risk.
Patient support groups and advocacy organizations can provide valuable resources and support.