Phenylketonuria (PKU)

Cindy Lee

autosomal recessive metabolic generic disorder

Mutation in the gene for phenylalanine hydroxylase (PAH) a hepatic enzyme

PAH is used to metabolize phenylalanine (Phe –amino acid) into tyrosine.

The mutation in the enzyme makes the enzyme nonfunctional

WHAT IS IT?

When phenylalanine piles up, it turns into phenylpyruvate, which is also known as phenylketone can be detected in your pee

WHEN LEFT UNTREATED…May lead to:

mental retardationSeizuresSerious medical problems

DETECTION TECHNIQUES

Babies are screened for PKU soon after birth in developed nations

Screening is done by: Guthrie Test (bacterial inhibition assay)Immunoassays (fluorometric/photometric

detection)Tandem Mass Spectrometry (MS/MS)

Amino acid measurement

SCREEN TESTING

Routine newborn screening test is typically performed 2-7 days after birthUses samples drawn by neonatal heel prick

The disease may be present with seizures, albinism, and a musty odor (due to phenylacetate produced in sweat and urine)

Usually, tests are repeated at two weeks of age In order to verity the initial test

NEONATAL HEEL PRICK

ALBINISM

LACK OF TREATMENT = Although generally healthy at birth, they

fail to attain early developmental milestonesDevelop microcephalyDemonstrate progressive impairment of cerebral function

Later in life:Show hyperactivityEEG abnormalitiesSeizuresSevere learning disabilities “musty/mousy” odor of skin, hair, weat, and urine tendency towards hypopigmentation tendency towards eczema

IN CONTRAST…

affected children who are treatedLess possibility for neurological

problems Less likely to have seizuresLess likely to have mental retardation

INCIDENCESCOUNTRY RATIO

TURKEY 1 IN 2,600

IRELAND 1 IN 4,500

NORWAY 1 IN 13,000

UNITED STATES 1 IN 15,000

CHINA 1 IN 18,000

INDIA 1 IN 18,300

KOREA 1 IN 41,000

JAPAN 1 IN 120,000

FINLAND <1 IN 100,000

NORMAL PKU

PROTEIN FROM FOOD

PROTEIN FROM MUSCLE

PROTEIN FROM FOOD

PROTEIN FROM MUSCLE

AMINO ACID AMINO ACID

PHENYLALANINE PHENYLALANINEOTHER AMINO

ACIDSOTHER AMINO

ACIDS

PHENYLALANINE HYDROXYLASE

PHENYLALANINE HYDROXYLASE

TYROSINE TYROSINE

BUILD UP OF PHE

HEALTH PROBLEMS