Phenylalanine hydroxylase deficiency, also known as phenylketonuria (PKU), is a condition where the body struggles to process the amino acid phenylalanine due to a lacking enzyme.
This deficiency can lead to harmful levels of phenylalanine if not treated. The severity of the condition varies, and if left untreated, it can cause irreversible intellectual disability, seizures, developmental delay, and behavioral issues. There are different forms of PAH deficiency, with the classic form being the most severe. Individuals with classic PAH deficiency produce little to no phenylalanine hydroxylase, putting them at risk of high phenylalanine levels. Without prompt diagnosis and a special diet, symptoms like intellectual disability, seizures, and behavioral problems may occur. Milder forms, known as variant PKU or non-PKU hyperphenylalaninemia, have fewer symptoms but still pose risks to mental development if phenylalanine intake is not monitored.
Treatment involves managing phenylalanine levels through a low-protein diet. Individuals with classic PAH deficiency must strictly follow this diet, while those with milder forms may consume small amounts of phenylalanine. Special formulas and blood tests help regulate phenylalanine levels, and this treatment often continues throughout life. It’s crucial to avoid aspartame, an artificial sweetener containing phenylalanine, and pregnant women with PAH deficiency should be extra cautious to prevent birth defects.
PKU is caused by pathogenic (disease-causing) variants in the PAH gene and exhibits autosomal recessive inheritance. This means that both parents must be carriers to have a 25% chance to have a child with the condition. The risk of being a carrier is based on a person’s ancestry or ethnic background. Individuals of Ashkenazi Jewish descent have a 1 in 225 chance to be a carrier of PHD.
Resources:
Updated November 2023
