Not all children with high phenylalanine have PKU ! (case study).
Rania; Term Female , was born at 4th June 2021
by Cesarean section
• Mother: G5 P4 A0.
• Mother: No complications during pregnancy, with
good antenatal care.
• No complications during delivery.
• At birth: Weight:3kg . Length: 48 cm. OFC: 34 cm.
• Newborn screening for genetic disease
diagnosed with Phenylketonuria.
• After one month: she was in good general
condition, active, with exclusive breastfeeding (
special formula was not available ), good
nutritional assessment according to age,
Length, weight and good cranial circumference.
No respiratory or neurological changes.
• phenylalanine in the blood was not so high 12
mg/dL ? Therefore we decided to think again
• Most important step is to send to genetic test.
Farther History …..
• Nothings were significant in history apart
from Family History
• Father 39 years , Mother 32 years old
(cousins) no medical history, allergy or chronic
• Family with a history of four deaths, as
On further enquiry
• By close observation and contentious
assessment of patient regarding history, physical
examination and farther investigations (Pending
genetic test ….)
after second month; recurrent attacks of cough
and shortness of breath.
frequent passage of bulky, offensive stool and
later with failure of gaining weight
This is GIT & Respiratory problem ??
• (BH4) deficiency: Kuvan (sapropterin
dihydrochloride) & PKU Formula.
o For Cystic fibrosis (CF):
o pancreatic enzyme replacement therapy 3000
lipase units prior to each feeding.
o extra salt (1/8 teaspoon of table salt)
o We also administer fat-soluble vitamins A, D E
Outcome and follow-up:
• The patient's blood phenylalanine levels
gradually normalized after treatment BUT
• She did not gain weight and Diarrhea become
more sever with sever lower respiratory tract
infection & and frequent intubation in PICU
• Unfortunately the baby Rania passed away on
29 January 2021 …
• (BH4) deficiency should be considered in a
patient diagnosed with PKU who presents
• We recommend the routine use of Genetic
test for any patient with PKU who developed
progressive neurological deterioration despite
early dietary management.
• Phenylketonuria (PKU), which was first reported
by in 1934, is one of the most common inborn
errors of metabolism with an estimated
prevalence of 1 in 10,000 in the European
• PKU is caused by the deficiency of phenylalanine
hydroxylase, which catalyzes the hydroxylation of
phenylalanine to generate tyrosine.
• As a result, phenylalanine will accumulate to toxic
levels causing irreversible intellectual disability
• Tetrahydrobiopterin (BH4) is an essential cofactor for the
hydroxylation of aromatic amino acids phenylalanine,
tyrosine, and tryptophan.
• Therefore, tetrahydrobiopterin deficiency results in
hyperphenylalaninemia as well as dopamine and serotonin
depletion in the central nervous system.
• The enzyme 6-pyruvoyltetrahydropterin synthase catalyzes
the second step of de novo synthesis of
tetrahydrobiopterin, and its deficiency is the most frequent
cause of tetrahydrobiopterin metabolism disorders.
• (BH4) that was first identified in the 1960s.
• Disorders of BH4 metabolism account for only 1%
to 2% of patients with hyperphenylalaninemia
in Europeans, whereas they are more common in
some other ethnic groups.
• For example, BH4 deficiency accounts for more
than 10% of hyperphenylalaninemia patients in
some countries in East Asia, reaching up to one-
third of cases in some reports.
• In a cross sectional study from Iran, 76 of 617
(12%) with hyperphenylalaninemia have BH4