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 do you test for BH4 deficiency?
Pterins, neurotransmitter metabolites and folates can be measured in cerebrospinal fluid (CSF). These tests can help to distinguish tetrahydrobiopterin deficiencies from one another and to assess the potential severity of the disease. Molecular genetic testing can confirm a diagnosis of these disorders.
What is BH4 used for?
BH4 is a naturally-occurring compound that serves as a cofactor for PAH and other enzymes. Kure et al. (1999) and a number of subsequent studies have found that BH4 supplementation is effective in lowering blood serum phe levels in a subset of individuals with PKU (for review, see Hegge et al., 2009).
Is BH4 deficiency the same as PKU?
BH4 deficiencies are grouped with phenylketonuria (PKU), which is an inborn error of protein metabolism that results from an impaired ability to metabolize the essential amino acid Phe. Similar to PKU, BH4 deficiencies negatively affect developmental function.
How does the body make BH4?
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 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.
What is tbh condition?
Tetrahydrobiopterin deficiency (THBD, BH4D) is a rare metabolic disorder that increases the blood levels of phenylalanine. Phenylalanine is an amino acid obtained normally through the diet, but can be harmful if excess levels build up, causing intellectual disability and other serious health problems.
How does BH4 help PKU?
How can it help treat PKU? The PAH enzyme consists of four identical pieces. If there is a fault in any of the pieces, they cannot fit together and work properly. BH4 may help these pieces fold correctly so that they can come together and form a more functional PAH enzyme.
What enzyme converts dopa to dopamine?
DOPA is converted to dopamine by aromatic amino acid decarboxylase. Dopamine-β-hydroxylase hydroxylates dopamine to norepinephrine, which is methylated to epinephrine by phenylethanolamine N-methyltransferase. Tyrosine hydroxylase is the rate-limiting enzyme of the pathway.
How does tyrosine work?
Supplementing with tyrosine is thought to increase levels of the neurotransmitters dopamine, adrenaline and norepinephrine. By increasing these neurotransmitters, it may help improve memory and performance in stressful situations (4). Summary Tyrosine is an amino acid that the body produces from phenylalanine.
What is BH4 chemistry?
Description. Borohydride is a boron hydride. ChEBI. A class of inorganic or organic compounds that contain the borohydride (BH4-) anion.
What is BH4 loading test?
The most used method is the BH4 loading test. Historically this test was performed at neonatal age, immediately after neonatal screening and aimed to distinguish hyperphenylalaninemic patients with PAH deficiency and patients with a BH4 deficiency [10, 11].
What is phenylalanine made from?
Good sources of phenylalanine are eggs, chicken, liver, beef, milk, and soybeans. Another common source of phenylalanine is anything sweetened with the artificial sweetener aspartame, such as diet drinks, diet foods and medication; the metabolism of aspartame produces phenylalanine as one of the compound’s metabolites.
Can you supplement BH4?
Rather, studies have shown that MTHF supplementation can increase BH4 levels by preventing its oxidation into BH2 and by supplementing BH4 activity with NOS enzymes further preventing its degradation.
Does royal jelly have BH4?
BH4 plays a critical role in both neurotransmitter and nitric oxide production. This formulation contains Royal Jelly, which has naturally occurring BH4, folinic acid (as calcium folate and 5-MTHF 2:1), 6S-5-MTHF, SAMe and lithium to support production of BH4.
How common is the Mthfr gene mutation?
MTHFR gene polymorphisms are common worldwide, with an estimated 25 percent of Hispanics and 10 to 15 percent of North American whites having the 677C>T polymorphism in both copies of the gene. Most people with MTHFR gene polymorphisms do not have neural tube defects, and their children are also typically unaffected.