Phenylalanine hydroxylase deficiency

Phenylalanine Hydroxylase Deficiency
Synonyms	N/A
Pronounce	N/A
Specialty	N/A
Symptoms	Intellectual disability, seizures, behavioral problems, skin rashes
Complications	N/A
Onset	Infancy
Duration	Lifelong
Types	N/A
Causes	Mutations in the PAH gene
Risks
Diagnosis	Newborn screening, Blood test
Differential diagnosis	N/A
Prevention	N/A
Treatment	Dietary management, Sapropterin
Medication	N/A
Prognosis	Good with treatment
Frequency	1 in 10,000 to 15,000 births
Deaths	N/A

Phenylalanine hydroxylase deficiency is a genetic disorder characterized by the body's inability to properly metabolize the amino acid phenylalanine. This condition is most commonly known as Phenylketonuria (PKU), which is the most severe form of the disorder.

Pathophysiology

Phenylalanine hydroxylase deficiency is caused by mutations in the PAH gene, which encodes the enzyme phenylalanine hydroxylase. This enzyme is responsible for converting phenylalanine into tyrosine, another amino acid. When phenylalanine hydroxylase is deficient or absent, phenylalanine accumulates in the blood and other tissues, leading to toxic effects on the brain and other organs.

Genetics

The disorder is inherited in an autosomal recessive pattern, meaning that an individual must inherit two defective copies of the PAH gene, one from each parent, to be affected. Carriers, who have one normal and one mutated gene, typically do not show symptoms but can pass the mutated gene to their offspring.

Clinical Presentation

Symptoms of phenylalanine hydroxylase deficiency can vary depending on the severity of the enzyme deficiency. Classic PKU, the most severe form, presents with symptoms such as:

• Intellectual disability
• Seizures
• Behavioral problems
• Skin rashes (eczema)
• A musty odor in breath, skin, or urine due to phenylacetate accumulation

Diagnosis

Phenylalanine hydroxylase deficiency is typically diagnosed through newborn screening programs, which measure the levels of phenylalanine in the blood. If elevated levels are detected, further confirmatory tests, such as genetic testing for PAH mutations, are performed.

Management

The primary treatment for phenylalanine hydroxylase deficiency is a phenylalanine-restricted diet, which involves limiting the intake of high-protein foods and using special medical formulas to provide essential nutrients. In some cases, the drug sapropterin dihydrochloride, a synthetic form of the cofactor tetrahydrobiopterin (BH4), may be used to enhance residual enzyme activity.

Prognosis

With early diagnosis and proper dietary management, individuals with phenylalanine hydroxylase deficiency can lead normal lives with normal intellectual development. However, untreated or poorly managed cases can result in severe intellectual disability and other neurological problems.

Epidemiology

Phenylalanine hydroxylase deficiency occurs in approximately 1 in 10,000 to 15,000 newborns worldwide, with varying prevalence among different populations.

See Also

• Phenylketonuria
• Metabolic disorder
• Amino acid metabolism

External Links

• [National PKU Alliance]
• [Genetics Home Reference - Phenylalanine Hydroxylase Deficiency]