phenylalanine hydroxylase deficiency

What is Phenylalanine Hydroxylase Deficiency?

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. It is caused by harmful genetic changes in the PAH gene. Phenylalanine is found in proteins and other certain foods. If individuals with PAH deficiency do not get treatment, phenylalanine can accumulate to harmful levels, which can cause irreversible intellectual disability, seizures, developmental delay, and behavioral problems.

PAH deficiency causes a spectrum of disorders ranging from severe to nearly asymptomatic. The severity depends on the level of phenylalanine in the blood. It can be difficult to predict how severely affected a child will be based on the harmful genetic changes they carry. Children with any form of PAH deficiency should be evaluated by a specialist immediately after birth.

Classic Form

Classic PAH deficiency is the most common and severe form. Individuals with classic PAH deficiency produce little to no phenylalanine hydroxylase and are at risk for accumulating high levels of phenylalanine in their blood.

If PAH deficiency is not promptly diagnosed and treated with a special diet, intellectual disability will occur, along with several other symptoms. These include a small head, seizures, behavioral problems, a "mousy" or "musty" odor, abnormal gait, low bone density, and red, itchy skin (eczema). Symptoms are avoidable if the proper diet is instituted shortly after birth and maintained throughout life.

Mild Forms

Individuals who produce higher amounts of phenylalanine hydroxylase may have milder forms of PAH deficiency but are still at risk of developing the symptoms associated with classic PAH deficiency. Other names for the mild form include variant PKU or non-PKU hyperphenylalaninemia. Though the symptoms may be milder, there is still a risk for impaired mental development if the child's intake of phenylalanine is not monitored. Some individuals with mild PAH deficiency are able to tolerate a normal diet and do not require treatment. This will vary from person to person and must be determined by a medical professional based on the levels of phenylalanine in the person’s blood.

How common is Phenylalanine Hydroxylase Deficiency?

The prevalence of PAH deficiency is 1 in 10,000. It is more common in individuals of Turkish and Irish descent.

How is Phenylalanine Hydroxylase Deficiency treated?

The primary treatment for PAH is a low-protein diet. Given that the degree of enzyme deficiency varies among people with PAH deficiency, treatment must be individualized based on the levels of phenylalanine in the blood. An infant with any form of PAH deficiency should be evaluated immediately after birth to determine whether or not treatment is needed. A blood test can reveal the amount of functioning phenylalanine hydroxylase in the body, indicating the amount of phenylalanine the person can safely consume.

While individuals with classic PAH deficiency must adhere to a strict low-phenylalanine diet, others with milder forms can safely consume small amounts. For some, treatment may not even be necessary. Individuals on a low-protein diet must also take dietary supplements that include essential amino acids but do not include phenylalanine.

Generally speaking, a diet low in protein and free from phenylalanine is essential to preserve mental function in a person with classic PAH deficiency. Phenylalanine-free formulas are available for infants. Maintaining appropriate levels of phenylalanine in the brain can be achieved through blood testing and diet adjustment. Medical professionals must closely supervise this. In most cases, this special diet must be maintained for life.

Individuals with any form of PAH deficiency should avoid consuming aspartame, an artificial sweetener containing phenylalanine.

Women with PAH deficiency who become pregnant must be careful to maintain safe levels of phenylalanine to avoid birth defects in their children. Ideally, this begins before conception.

A few medications are available that the FDA has approved to treat patients with PAH deficiency. These medications have allowed some patients to relax their dietary restrictions. The medications do not work for all PAH patients, and some patients experience unpleasant side effects.

What is the prognosis for a person with Phenylalanine Hydroxylase Deficiency?

If an individual with PAH deficiency is treated early and consistently, the prognosis can be excellent. Many with PAH deficiency have gone on to lead normal lives with average intelligence and a normal lifespan. If treatment does not begin early or is not adequately maintained, a person with a more severe form of PAH deficiency is at risk for severe and irreversible brain damage.

Individuals with mild PAH deficiency may lead a normal life without treatment.