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CASE FILES: BIOCHEMISTRY
A N SW E R S TO C A SE 38: P H E N Y L K E T O N U R IA (PK U )
Summary:
A 1-year-old girl bom outside the United States with developmen-
tal delays, hypotonia, hypopigmentation, and foul smelling urine.
Likely Diagnosis: Phenylketonuria (PKU)
Biochemical basis of hypopigmentation: Phenylalanine is competitive
inhibitor of tyrosinase (key enzyme in melanin synthesis)
C L IN IC A L C O R R E L A T IO N
Elevated phenylalanine can be caused by a variety of different enzyme deficien-
cies resulting in impaired conversion of phenylalanine to tyrosine. The most
common deficiency is in phenylalanine hydroxylase (autosomal recessive)
resulting in the classic picture of PKU. Two other enzyme deficiencies leading
to PKU include dihydropteridine reductase and
6
-pyruvoyl-tetrahydropterin
synthase, an enzyme in the biosynthetic pathway of tetrahydrobiopterin. With
PKU, the baby appears normal at birth but then fails to reach normal develop-
mental milestones. If unrecognized, the child will develop profound mental
retardation and impairment of cerebral function. A mousy odor of the skin, hair,
and urine can often be detected clinically. Areas of hypopigmentation develop
secondary to the disruption of melanin synthesis. In the United States, all chil-
dren are screened for PKU in hopes to prevent the serious life-long complica-
tions.
Treatment consists of dietary modifications
with limitation of
phenylalanine intake and supplementation of tyrosine. The diagnosis of PKU
and initiation of diet modification needs to be implemented prior to 3 weeks of
age to prevent mental retardation and the other classic signs of PKU.
A PPR O A C H TO PH E N Y L K E T O N U R IA
O bjectives
1
.
Describe the biochemical conversion of phenylalanine to tyrosine.
2.
Describe the biochemical events that occur when conversion of pheny-
lalanine to tyrosine is inhibited.
D efinitions
Hypopigmentation: Lack of color in skin or hair due to the absence or low
quantity of the skin and hair pigment melanin, a product of tyrosine (and
phenylalanine) metabolism.
Tetrahydrobiopterin: A four-electron-reduced form of the reducing agent
biopterin required to supply electrons to phenylalanine hydroxylase for
conversion of phenylalanine to its hydroxylated product, the amino acid
tyrosine.
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