6-Pyruvoyl-Tetrahydrobiopterin Synthase Deficiency
What else is it called?
- 6-PTS Deficiency
- Hyperphenylalaninemia due to 6-pyruvoyl-tetrahydropterin synthase deficiency
- Hyperphenylalanemia, BH4-deficient, A
- PTPS Deficiency
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What causes it?
This disorder is caused by a defect in the PTS gene which is needed to produce an enzyme called 6-pyruvoyltetrahydropterin synthase. The enzyme is needed to make a molecule called tetrahydrobiopterin (BH4), which is needed to convert the amino acid phenylalanine into tyrosine. The fault in the gene means that the enzyme cannot function properly and as a result, not enough tetrahydrobiopterin is produced. This means that the body is unable to convert phenylalanine and it instead builds up and becomes toxic.
Tetrahydrobiopterin is also involved in the production of neurotransmitters, which are chemicals that send messages between the nerve cells in the brain. Therefore, if the body does not produce enough tetrahydrobiopterin, there will be low levels of the neurotransmitters dopamine and serotonin in the central nervous system
How common is it?
We do not know exactly how many people are affected by this condition. It has been reported in patients of different ethnicities and has an increased prevalence in individuals of Asian ancestry.
What are the signs and symptoms?
Signs and symptoms of this condition can vary greatly amongst individuals. Most cases (approximately 80%) present with the severe form, also known as the “typical” form.
Clinical findings are often prevalent at birth. If untreated, neurological symptoms are likely to occur around the age of 4 to 5 months of age.
- Slowing of thought processes and a reduction of physical movements (psychomotor retardation)
- · Low muscle tone
- Co-ordination, balance and speech problems (ataxia)
- Small head size (microcephaly)
- Drowsiness, lethargy
- Abnormal movements; rapid or slow involuntary movements, twisting and repetitive movements or abnormal fixed postures, and/or muscle spasms – some causing backward arching of the head, neck, and spine
- Low body temperature (hypothermia) and/or high body temperature (hyperthermia)
- Excessive production of saliva (hypersalivation)
- Swallowing difficulties
- Learning difficulties and behavioural problems
- Delays in reaching developmental milestones#
In the “atypical” form where symptoms are less severe, the condition may range from having intermittently high levels of phenylalanine (hyperphenylalaninemia) to having a mild form of the condition which develops into the severe form.
How is it diagnosed?
This disorder should be suspected following a positive screening result for Phenylketonuria (PKU), especially if the levels of phenylalanine are moderately raised. Diagnosis can be confirmed via specialised blood and urine tests and genetic testing.
Can it be treated?
There is no cure for this disorder and management is lifelong. Treatment aims to reduce phenylalanine levels to normal range through a restricted phenylalanine diet (low protein diet) and/or prescribed tetrahydrobiopterin (BH4). Dietary management will be overseen by a specialist dietitian who will help you to understand the diet and plan recipes. Further medications (L-dopa/carbidopa and 5-hydroxytryptophan) may be used to improve the way the brain transmits messages between nerve cells. Other treatment is symptomatic and supportive.
Do my family need to be tested?
This disorder is inherited from both parents in an autosomal recessive inheritance pattern. This means that both parents are carriers of the disorder through their genes.
All genes come in pairs. Carriers of this disorder have one working PTS gene and one faulty gene. Children inherit one gene from each parent to make their pair. Whether you have this disorder depends on the genes you inherit:
- There is a 50% chance that the child will inherit one faulty and one working gene, which means they will also be a carrier.
- There is a 25% chance that the child will inherit two working genes and not inherit or carry the faulty gene.
- There is a 25% chance that the child will inherit two faulty genes, which means they will have the disorder.
If you think you, or somebody in your family, may have 6-PTS Deficiency, or that you may be a carrier, contact your medical team who may refer you for genetic testing.
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