What is a 6-pyruvoyl-tetrahydropterin synthase deficiency?
Abstract. Severe 6-pyruvoyl-tetrahydrobiopterin synthase deficiency is a tetrahydrobiopterin deficiency disorder that presents in infancy with developmental delay, seizures, and abnormal movements associated with hyperphenylalaninemia usually detectable by neonatal phenylketonuria screening programs.
What is 6-pyruvoyl-tetrahydropterin synthase?
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.
What is Ptps deficiency?
Definition. 6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency is one of the causes of malignant hyperphenylalaninemia due to tetrahydrobiopterin deficiency.
What is BH4 deficiency?
Collapse Section. Tetrahydrobiopterin deficiency is a rare disorder characterized by a shortage (deficiency) of a molecule called tetrahydrobiopterin or BH4. This condition alters the levels of several substances in the body, including phenylalanine.
How is BH4 deficiency treated?
Treatment of BH4 deficiencies consists of BH4 supplementation (2-20 mg/kg per day) or diet to control blood phenylalanine concentration and replacement therapy with neurotransmitters precausers (L-dopa/CarbiDOPA and 5-hydroxytryptophan), and supplements of folinic acid in DHPR deficiency.
Does BH4 deficiency cause PKU?
In Taiwan, 2-30% of cases of PKU are attributed to BH4 deficiency. In Turkey, which has the highest incidence of PKU in the world with approximately 1 case per 2600 births, 15% of cases are due to BH4 deficiency. In Saudi Arabia, 66% of PKU cases are due to BH4 deficiency.
What does Hyperphenylalaninemia mean?
Hyperphenylalaninemia is a hereditary metabolic disorder that causes elevated blood phenylalanine (Phe). Hyperphenylalaninemias are classified as Phenylketonuria PKU (Phe > 6 mg/dL) or mild hyperphenylalaninemia (mHPA) (Phe 2–6 mg/dL).
What is SPR disease?
SPR deficiency. Sepiapterin reductase deficiency is an inherited pediatric disorder characterized by movement problems, and most commonly displayed as a pattern of involuntary sustained muscle contractions known as dystonia.
What is BH4 supplement?
Tetrahydrobiopterin (BH4) is a naturally occurring essential cofactor for the conversion of a nitrogen component of l-arginine to NO by endothelial nitric oxide synthase (eNOS).
How do you test for BH4?
Diagnosis is based on the symptoms, clinical exam, and blood and urine tests. BH4 deficiency is sometimes diagnosed based on the results of an abnormal newborn screening test.
Where is BH4 from?
BH4 is made from the molecule GTP (guanosine triphosphate). GTP is converted into BH4 in three stages, which are catalysed (in order) by the enzymes GTPCH, PTPS and SR. These enzymes are coded for, respectively, by the GCH1, PTS and SR genes. Interestingly, rare mutations in these genes can lead to deficiency of BH4.
How is BH4 produced?
BH4 is formed de novo from GTP, via a sequence of enzymatic steps carried out by GTP cyclohydrolase I (GTPCH), 6-pyruvoyl tetrahydropterin synthase (PTPS) and sepiapterin reductase (SR) [15].
What causes 6-pyruvoyl-tetrahydropterin synthase deficiency ( PTPs )?
6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency is one of the causes of malignant hyperphenylalaninemia due to tetrahydrobiopterin deficiency.
When to suspect PTPS deficiency in an infant?
PTPS deficiency should be suspected in all infants with a positive neonatal screening test for phenylketonuria, especially when hyperphenylalaninemia is moderate.
Are there any mutations in the PTS gene?
Thony et al. (1994) identified mutations in the PTS gene (e.g., 612719.0001 – 612719.0003) in patients with BH4-deficient hyperphenylalaninemia (HPABH4A; 261640 ). Oppliger et al. (1997) identified 4 novel mutations in 4 Italian families with BH4-deficient hyperphenylalaninemia due to PTS deficiency.
How to treat phenylalaninemia and PTPS deficiency?
PTPS deficiency is an autosomal recessive genetic disorder. Treatment attempts to bring phenylalaninemia levels back to normal (diet with restricted phenylalanine intake or prescription of tetrahydrobiopterin) and to restore normal monoaminergic neurotransmission by administering precursors (L-dopa/carbidopa and 5-hydroxytryptophan).