phenylketonuria

Phenylketonuria (PKU) is a metabolic disorder and the most common inborn error of amino acid metabolism. It is caused by pathogenic variants in the PAH gene, which normally helps convert phenylalanine into tyrosine. Untreated, the condition is characterized by a range of intellectual and developmental disabilities. Newborn screening is routinely performed for PKU, and because precise prevalence estimates are not well established, the exact number of affected individuals remains unclear.

In untreated individuals, PKU is associated with neurological impairments that can manifest as mild to severe intellectual disability along with learning difficulties. In addition, laboratory evaluations reveal characteristic biochemical markers such as elevated urinary gamma-glutamylphenylalanine levels and increased hippuric acid in the urine. Not all individuals experience all features, and severity varies considerably. Early intervention is important to prevent the development of these complications.

Phenylketonuria results from pathogenic variants in the PAH gene, which encodes the enzyme phenylalanine hydroxylase. This enzyme is responsible for converting the amino acid phenylalanine into tyrosine, and its deficiency leads to the accumulation of phenylalanine and its metabolites. The condition is inherited in an autosomal recessive manner, meaning that an affected individual has inherited two altered copies of the gene, one from each parent. Genetic counseling is recommended to help families understand the implications for family planning.

Currently, management focuses on supportive care and symptom management. Although there are no FDA-approved treatments specifically for PKU, early identification allows for interventions that can help mitigate neurological damage. Treatment is tailored to the individual and typically involves a multidisciplinary team that may include nutritional specialists, developmental experts, and genetic counselors. Patients should discuss treatment options with their healthcare team to determine the most appropriate management strategy for their situation.

With current standards of care, outcomes for individuals with PKU vary widely. In the absence of treatment, the condition is associated with significant intellectual and developmental challenges, whereas early detection through newborn screening followed by appropriate management can improve long-term outcomes. The course of the condition is highly variable, and while early interventions help reduce the risk of neurological complications, individual experiences differ considerably. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with specialists familiar with this condition, and genetic counseling can provide valuable guidance for family planning.

Phenylketonuria remains an active area of research, with numerous ongoing clinical trials investigating new approaches to treatment. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team about eligibility for emerging studies.