Summary about Disease
6-Pyruvoyltetrahydropterin synthase (PTPS) deficiency is a rare, inherited metabolic disorder that affects the production of tetrahydrobiopterin (BH4). BH4 is a crucial cofactor for several enzymes involved in the synthesis of neurotransmitters like dopamine, norepinephrine, epinephrine, and serotonin, as well as nitric oxide. PTPS deficiency leads to a build-up of phenylalanine in the blood (hyperphenylalaninemia) and a deficiency of these vital neurotransmitters. This can result in neurological problems.
Symptoms
Symptoms vary in severity, depending on the type of PTPS deficiency and the degree of neurotransmitter deficiency. Common symptoms include:
Progressive neurological deterioration
Developmental delay
Seizures
Hypotonia (low muscle tone)
Movement disorders (dystonia, rigidity)
Irritability
Sleep disturbances
Feeding difficulties
Microcephaly (small head size)
Hyperphenylalaninemia detected on newborn screening
Causes
PTPS deficiency is caused by mutations in the PTS gene. This gene provides instructions for making the 6-pyruvoyltetrahydropterin synthase enzyme. Mutations in this gene disrupt the enzyme's function, leading to a deficiency of BH4. It is inherited in an autosomal recessive manner, meaning that an affected individual must inherit two copies of the mutated gene (one from each parent).
Medicine Used
Treatment focuses on replacing deficient neurotransmitters and managing hyperphenylalaninemia. Medications commonly used include:
Sapropterin dihydrochloride (Kuvan): A synthetic form of BH4. It can improve phenylalanine levels in some individuals.
L-Dopa: A precursor to dopamine, used to replace dopamine deficiency.
Carbidopa: Administered with L-dopa to prevent its breakdown in the bloodstream before it reaches the brain.
5-Hydroxytryptophan (5-HTP): A precursor to serotonin, used to replace serotonin deficiency.
Folinic acid: Can be helpful in some patients with specific forms of BH4 deficiency.
Dietary Management: A low-phenylalanine diet is crucial for managing hyperphenylalaninemia.
Is Communicable
No, PTPS deficiency is not communicable. It is a genetic disorder, caused by inheriting mutated genes from parents. It cannot be spread from person to person.
Precautions
Since PTPS deficiency is a genetic condition, prevention focuses on genetic counseling and testing for families with a history of the disorder. Careful monitoring and adherence to treatment protocols (medication and diet) are crucial for managing the condition and minimizing complications. Newborn screening for phenylketonuria (PKU) can help identify affected individuals early.
How long does an outbreak last?
PTPS deficiency is not an outbreak; it is a chronic genetic condition. The symptoms persist throughout the individual's life, although their severity can be managed with appropriate treatment.
How is it diagnosed?
Diagnosis typically involves:
Newborn screening: Elevated phenylalanine levels on newborn screening.
Blood and urine tests: To measure levels of phenylalanine, biopterin, neopterin, and other metabolites.
Dihydropteridine reductase (DHPR) assay: To rule out DHPR deficiency, another cause of BH4 deficiency.
Molecular genetic testing: To identify mutations in the PTS gene.
Neurotransmitter metabolite analysis: Analysis of cerebrospinal fluid (CSF) to measure levels of neurotransmitter metabolites (HVA, 5-HIAA) helps differentiate between different types of BH4 deficiencies and guides treatment.
BH4 loading test: Assess response to synthetic BH4.
Timeline of Symptoms
The onset and progression of symptoms vary. Some individuals may show symptoms in early infancy, while others may have a delayed onset. A typical timeline might include:
Newborn period: Detection of elevated phenylalanine levels on newborn screening.
Infancy: Hypotonia, feeding difficulties, developmental delay, seizures.
Childhood: Movement disorders, intellectual disability, behavioral problems.
Throughout life: Progressive neurological deterioration if left untreated. With early diagnosis and treatment, the severity of symptoms can be reduced.
Important Considerations
Early diagnosis and treatment are crucial to minimize neurological damage and improve outcomes.
Management requires a multidisciplinary approach involving physicians, dietitians, genetic counselors, and other specialists.
Lifelong monitoring and adherence to treatment are essential.
Genetic counseling is recommended for families with a history of PTPS deficiency to assess recurrence risks and discuss reproductive options.
Even with optimal treatment, some individuals may still experience some degree of neurological impairment.