What is hyperphenylalaninemia?

It is the most common amino acid metabolism disorder, which can lead to delayed intellectual development in children. It is the first treatable and preventable genetic disease in medical history. Among the four diseases screened by heel blood collection in newborns after birth, phenylketonuria is a type of hyperphenylalaninemia.

Which department should be consulted for hyperphenylalaninemia?

English name: hyperphenylalaninemia, HPA.

Alias: phenylketonuria, mouse urine disease.

Departments for consultation: neonatology, pediatric neurology, pediatrics, neurology.

What causes hyperphenylalaninemia?

It is an autosomal recessive genetic disease caused by pathogenic gene mutations. It is divided into two major types based on the affected enzyme: phenylalanine hydroxylase (PAH) deficiency and tetrahydrobiopterin (BH4) deficiency.

Which groups are commonly affected by hyperphenylalaninemia?

It is commonly seen in newborns with a family history of the disease.

What are the main symptoms and manifestations of hyperphenylalaninemia?

Clinical manifestations vary depending on the type. Symptoms gradually appear 3–4 months after birth, including lighter skin and hair color, a mouse-like odor in sweat and urine, and delayed intellectual development, microcephaly, increased drooling, and possible seizures or behavioral and personality abnormalities as the child grows older.

BH4 deficiency may also present with movement disorders and dystonia.

How is hyperphenylalaninemia diagnosed?

Diagnosis is confirmed by significantly elevated blood phenylalanine levels and a phenylalanine-to-tyrosine ratio greater than 2.0, following differential diagnosis. Genetic testing to identify mutations can not only confirm the diagnosis but also determine the type of hyperphenylalaninemia.

How is hyperphenylalaninemia treated?

Early treatment is crucial, and lifelong therapy is recommended. Personalized low-phenylalanine diets remain the primary treatment. Since phenylalanine is an essential amino acid, blood levels must be monitored regularly to prevent deficiency. BH4 deficiency also requires supplementation with BH4 or L-dopa replacement therapy.

What is the prognosis for hyperphenylalaninemia?

The prognosis depends on disease severity, timing of treatment, and patient compliance. Most individuals can achieve normal or near-normal intellectual and physical development, allowing them to attend school, work, marry, and have children. A proper diet is key to improving outcomes.

How can hyperphenylalaninemia be prevented?

This disease is preventable and treatable, with prevention being the priority. Avoid consanguineous marriages, ensure timely newborn screening, and pursue early diagnosis and treatment.

Those with a clear family history can undergo genetic testing before conception.

Avoid foods high in phenylalanine, such as meat, fish, and soy products.