Does BH4 deficiency cause PKU?

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.

When there is a deficiency of phenylalanine hydroxylase?

Phenylalanine hydroxylase deficiency (PAH deficiency), also called phenylketonuria (PKU), is an inherited disease in which the body cannot properly process the amino acid phenylalanine due to a deficient enzyme called phenylalanine hydroxylase.

What is BH4 PKU?

Recently, sapropterin dihydrochloride, a synthetic form of tetrahydrobiopterin (BH4), has been introduced as a supplemental treatment to dietary phe control for PKU. BH4 is a naturally-occurring compound that serves as a cofactor for PAH and other enzymes.

What would happen if the enzyme phenylalanine hydroxylase was missing?

The most severe form of the disorder is called classic PKU. The enzyme needed to convert phenylalanine is missing or severely reduced, resulting in high levels of phenylalanine and severe brain damage. Less severe forms of PKU.

What can you eat on a PKU diet?

The diet for PKU consists of a phenylalanine-free medical formula and carefully measured amounts of fruits, vegetables, bread, pasta, and cereals. Many people who follow a low phenylalanine (phe) food pattern eat special low protein breads and pastas.

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.

How common is phenylalanine hydroxylase deficiency?

Phenylalanine hydroxylase deficiency is an autosomal recessive disorder that results in intolerance to the dietary intake of the essential amino acid phenylalanine. It occurs in approximately 1:15,000 individuals.

Where is phenylalanine hydroxylase found in the body?

liver
Phenylalanine hydroxylase (PAH) is expressed in the liver and kidney. Mutations in the gene that expresses PAH can lead to phenylketonuria, a serious metabolic disease. PAH is the enzyme that metabolizes excess phenylalanine.

Which enzyme is responsible for metabolizing phenylalanine?

Phenylalanine hydroxylase
Phenylalanine hydroxylase is responsible for the conversion of phenylalanine to another amino acid, tyrosine. The enzyme works with a molecule called tetrahydrobiopterin (BH4) to carry out this chemical reaction.

Can you eat potatoes with PKU?

Vegetables: Starchy vegetables like white, sweet, purple potatoes (and fries), winter squash, corn, and peas should be eaten sparingly. Most other fresh or frozen vegetables are low in phenylalanine with the exception of the ones on the non-compliant list.

What causes a deficient pah or BH4?

HPA is known to be caused by deficiencies of the enzyme phenylalanine hydroxylase ( PAH) or its cofactor tetrahydrobiopterin ( BH4 ). 1 The diagnosis of BH4 deficiencies is straight forward and should be investigated in all children with HPA.

What happens if you have a phenylalanine hydroxylase deficiency?

Phenylalanine hydroxylase (PAH) deficiency results in intolerance to the dietary intake of the essential amino acid phenylalanine and produces a spectrum of disorders.

How to diagnose PKU and BH4 deficiency?

PKU, phenylketonuria; GTPCH, GTP cyclohydrolase I; PTPS, 6-pyruvoyl-tetrahydropterin synthase; PCD, pterin-4a-carbinolamine dehydratase; DHPR, dihydropteridine reductase; BH4, tetrahydrobiopterin; DBS, dried blood spot; P, plasma; U, urine; n, normal An oral BH4 challenge (20 mg/kg body weight) is an additional useful test.

How is BH4 deficiency related to Fabry disease?

Shen et al (2017) established that BH4 deficiency also occurs in Fabry disease and may contribute to its pathogenesis via oxidative stress due to reduced antioxidant capacity of cells and NOS uncoupling. [ 16] BH4 deficiency is also associated with augmented inflammation and retinal microvascular degeneration. [ 17]