6-pyruvoyl-tetrahydropterin synthase deficiency

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What is 6-Pyruvoyl-Tetrahydropterin Synthase Deficiency?

6-pyruvoyl-tetrahydropterin synthase (PTPS) is a rare disorder caused by harmful genetic changes (mutations) in the PTS gene. The PTS gene is required to make tetrahydrobiopterin (BH4). Low levels of BH4 result in a condition called hyperphenylalaninemia, caused by toxic levels of the amino acid phenylalanine. Additionally, BH4 deficiency results in very low levels of chemicals that transmit impulses from one nerve cell to another in the brain (neurotransmitters).

Individuals with PTPS deficiency can have a variety of symptoms including neurological abnormalities (seizures and swallowing problems); low muscle tone (hypotonia); excess muscle tone (rigidity) in the arms and legs; loss of coordination or delayed motor development; delayed intellectual development; and temperature regulation problems. Infants with PTPS deficiency are often healthy at birth but quickly begin to show signs that they are not growing (failure to thrive). Additional symptoms generally appear within the first four to six months of life. A small head size (microcephaly) may develop in early infancy.

The symptoms of PTPS deficiency can vary widely and range from mild to severe. Twenty percent of individuals have the mild or atypical form. Individuals with the mild or atypical form of PTPS deficiency have moderate or momentary alterations in phenylalanine levels and normal levels of neurotransmitters.

How common is 6-Pyruvoyl-Tetrahydropterin Synthase Deficiency?

Several genes are known to cause tetrahydrobiopterin deficiency, which has an incidence of 1 in 1,000,000 births. PTPS is responsible for approximately 60% of tetrahydrobiopterin deficiency cases. The incidence of PTPS is more common among individuals of East Asian descent.

How is 6-Pyruvoyl-Tetrahydropterin Synthase Deficiency treated?

There is no cure for PTPS deficiency. Treatment will generally focus on reducing high phenylalanine levels through a specialized diet. Affected individuals may also need to take BH4 supplements and other medications that help restore neurotransmitter levels. All individuals with PTPS deficiency will be followed by a metabolic specialist.

What is the prognosis for an individual with 6-Pyruvoyl-Tetrahydropterin Synthase Deficiency?

Early treatment of PTPS deficiency is important in reducing severe, irreversible damage to the brain. With treatment, some individuals may have healthy growth and development. However, affected individuals can still have symptoms such as seizures, developmental delay, and intellectual disability even with proper diet and medications.