Makindo Medical Notes.com

Early diagnosis and so phenylalanine avoidance can prevent sequelae

About

• Treatable autosomal recessive disease screened for after birth
• Seen in 1:10-20,000 live births
• High levels of phenylalanine cause problems
• Symptomatic disease rarely seen where there is a screening program and early dietary changes

Genetics

• Loss of function in the PAH gene which makes Phenylalanine hydroxylase
• PAH breaks down Phenylalanine and loss means build up

Aetiology

• Deficient Phenylalanine hydroxylase (Chromosome 12)
• Deficient cofactor tetrahydrobiopterin (Genes on Chromosome 10 and 4)
• There are milder Forms of Hyperphenylalaninaemia, Non-PKU Hyperphenylalaninaemia

Clinical

• Mental developmental issues, Hypopigmentation. Seizures develop
• Older untreated children become hyperactive with purposeless movements, rhythmic rocking, and athetosis.
• Have seborrheic or eczematoid rash, which is usually mild and disappears as the child grows older.
• These children have an unpleasant odour of phenylacetic acid, which has been described as musty or mousy.
• There are no consistent findings on neurologic examination. However, most infants are hypertonic with hyperactive deep tendon reflexes.
• About 25% of children have seizures, and more than 50% have electroencephalographic abnormalities.
• Microcephaly, prominent maxilla with widely spaced teeth, enamel hypoplasia, and growth retardation are other common findings in untreated children.

Investigations

• Raised Blood and Urine Phenylalanine levels and normal plasma tyrosine levels and normal cofactor (tetrahydrobiopterin) concentrations.
• Guthrie test: elevated phenylalanine levels by pricking the heel of a newborn infant on the second or third day of life
• EEG: 50% have an abnormal EEG.
• Can be diagnosed in pregnancy by CVS
• Cerebral white matter changes are seen in older patients and may reflect a combination of late diagnosis and dietary indiscretion.

Management

• Avoid Phenylalanine intake with support from dieticians with restriction of dietary phenylalanine, while ensuring sufficient for physical and neurological growth.
• Co-factor defects are treated with a diet low in phenylalanine and high in neurotransmitter precursors.
• If patient with PKU becomes pregnant diet must be strictly monitored.
• Even with dietary treatment, some degree of cognitive impairment is seen and can vary from gross impairment or changes detected on cognitive tests.