History and exam

Key diagnostic factors

common

presence of risk factors

Inherited as an autosomal-recessive disorder. There is a 1 in 4 (25%) risk of recurrence of PKU in future pregnancies for parents who already have a child with PKU.

If 1 of the parents has PKU and chooses a partner from within the general population, the risk of the disorder occurring in a child is ≤1% because the partner would have to be a carrier of a gene for PKU for this to occur.

positive newborn screen for PKU

Almost all patients are identified as the result of a positive newborn screening test.

Other diagnostic factors

uncommon

intellectual disability

These patients should be evaluated for PKU. Although treatment will not reverse intellectual disability, it may result in improved behaviour and reduction in psychiatric morbidity.

microcephaly

Acquired microcephaly is a common finding in patients with untreated or late-treated PKU but should not occur in patients adequately treated from birth. Congenital microcephaly is commonly observed in the maternal PKU syndrome, because fetal brain growth is impacted by high phenylalanine levels in the maternal circulation.

eczema

Eczema is common in patients with PKU who have poorly controlled blood phenylalanine levels.

light pigmentation of eyes and hair

Light pigmentation of the hair and eyes is commonly seen in untreated patients with classical PKU, and results from decreased melanin production.

seizures

Seizures are common in untreated or late-treated patients with PKU, but uncommon in those treated from birth.

mousy odour of urine

A mousy odour to the urine is noted in patients with untreated classical PKU due to the presence of phenyl ketones.

Risk factors

strong

family history of PKU

Inherited as an autosomal-recessive disorder. There is a 1 in 4 risk of recurrence of PKU in future pregnancies (25%) for parents who already have a child with PKU.

If 1 of the parents has PKU and chooses a partner from within the general population, the risk of the disorder occurring in a child is ≤1% because the partner would have to be a carrier of a gene for PKU for this to occur.

weak

white ancestry

Although the disorder is most common in non-Hispanic white people, it occurs in all ethnic groups.

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