Absent phenylalanine hydroxylase activity without phenylketonuria

Area of Science:

• Biochemistry
• Genetics
• Pediatrics

Background:

• Phenylketonuria (PKU) is an inherited metabolic disorder.
• It is caused by deficiency of the enzyme phenylalanine hydroxylase (PAH).
• Early diagnosis and dietary management are crucial to prevent intellectual disability.

Observation:

• A male infant presented with undetectable phenylalanine hydroxylase activity in liver tissue.
• Plasma phenylalanine levels were elevated, consistent with PKU, during breastfeeding.
• Development remained normal following a low-phenylalanine diet.

Findings:

• The infant did not manifest clinical symptoms of phenylketonuria despite absent PAH activity.
• Elevated phenylalanine levels normalized with dietary intervention.
• This suggests a potential disconnect between enzyme activity and clinical phenotype.

Implications:

• The findings challenge the assumption that undetectable PAH activity invariably leads to PKU.
• This case may necessitate a re-evaluation of diagnostic thresholds and screening protocols for PKU.
• Further research is needed to understand the mechanisms underlying this atypical presentation.