Phenylketonuria (PKU) Clinical Presentation

Updated: Nov 23, 2020
  • Author: Eric T Rush, MD, FAAP; Chief Editor: Luis O Rohena, MD, PhD, FAAP, FACMG  more...
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Most individuals with phenylketonuria (PKU) appear normal at birth. If an affected patient does not undergo newborn screening or has false-negative results (rare), progressive developmental delay is the most common presentation. Other findings in untreated children in later infancy and childhood may include vomiting, mousy odor, eczema, seizures, self-mutilation, and severe behavioral disorders.

The cohort of patients identified in the early days of newborn screening were begun on diet modification as neonates and continued on that diet until they were school-aged and were then generally transitioned to a normal diet. While these patients escaped the most severe manifestations of PKU, many described poor focus and deteriorating cognitive skills. Those same individuals who ceased dietary treatment in childhood may also have evidence of white matter changes visible on magnetic resonance imaging (MRI), and those patients may experience an intelligence quotient (IQ) decline of 10 points or more.


Physical Examination

The clinical manifestations of PKU are largely of historical interest, because the damaging features of the disease are virtually always prevented through early diagnosis and treatment. Skin findings are as follows:

  • Fair skin and hair – This is the most characteristic skin manifestation, resulting from impairment of melanin synthesis; it can be striking in Black and Japanese patients, although not all untreated patients are fair, and treated patients often have typical pigmentation

    Fair skin and hair resulting from impairment of me Fair skin and hair resulting from impairment of melanin synthesis.
  • Eczema (including atopic dermatitis)

  • Light sensitivity

  • Increased incidence of pyogenic infections

  • Increased incidence of keratosis pilaris

  • Decreased number of pigmented nevi

  • Sclerodermalike plaques

  • Hair loss [1]

Other manifestations of untreated PKU are as follows:

  • Intellectual disability (the most common finding overall)

  • Musty or mousy odor

  • Epilepsy (50%) [2]

  • Extrapyramidal manifestations (eg, parkinsonism)

  • Eye abnormalities (eg, hypopigmentation)



Subtle attention and performance deficits in organization and planning persist in treated patients. These deficits are in some cases related to phenylalanine levels and may interfere with academic achievement.

The incidence of neuropsychiatric disease in PKU appears to be higher than in the general population and includes increased risk of depression, anxiety, and inattention, among others. It has been shown that these symptoms are exacerbated by high phenylalanine levels and improved by lower phenylalanine levels. These findings underscore the need for lifelong diet maintenance. [18]