PHENYLKETONURIA (PKU)

1,2
Ponnusamy

Dr PK_BIOGEN INNO-VISION 2015

1
RN

3
B

Dr Kumar
Ms Jegathambigai1
and Ms Sindhu
Biochemistry & Genetics, International Medical School (IMS) Management & Sciencne University,
1
AIMST University School of Medicine, 08100 Kedah, Malaysia
2
ST Matthews University School of Medicine (SMU), Grand Cayman, Cayman Islands, BWI
3
Department of Biomedical Engineering, Vellore Institute of technology (VIT) Vellore, India
Abstract
PKU is a inborn error of Phenylalanine (PA) metabolism, the occurrence of PKU varies among ethnic groups and geographic regions 1
worldwide. In the United States, PKU occurs in 1 in 10,000 to 15,000 newborns. Infants with classic PKU are normal at birth but if
untreated show slow development, severe mental retardation, autistic symptoms, and loss of motor control. Children may have pale skin
and white-blonde hair. The neurotoxic effects relate to high levels of PA and not to the phenylketones (PK) from which the name of the
disease derives.

Objective: To delineate the molecular and biochemical basis of PKU, diagnosis and management as well to facilitate
USMLE preparatory Course: BIOGEN Reusable On-Line Resources for Large Group Teaching-Learning in Relatively
4
Short Time.
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Molecular-Biochemical Basis of the Disease /
Disorder: PKU is a metabolic disease
characterizied by accumulation of PA and its
by-products in the blood of fetuses and newborns.
PKU results from a defect in the enzyme
Diffusion-Weighted Imaging of White Matter
Pathophysiology
Abnormalities
in
Patients
with
PKU
Phenylalanine Hydroxylase (PAH), such that PA is
of PKU
not converted to Tyrosine. The alternative
Clinical Signs & Symptoms
conversion of PA to PPA causes accumulation of the
PKU &
Neuropathology
latter as a toxin in the CNS, which can lead to
severe mental retardation.
PKU
Phenotype

Klung & Cummings 1997

DEFICIENCY
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PKU

Musty Odor, Blue Eyes, Microcephaly &

Mental Retardation

Pleotropy of PKU
Dysmorphic Features
in Maternal PKU

Bridge to Pharmacology-Toxicology / Management: Diet low

in Phenylalanine, avoid aspartame, diet important during pregnancy.

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Contraindications:
Aspartame
(N-aspartyl-phenylalanine
methyl
2
ester), which is widely used as an artificial sweetner, must be strictly
avoided by Phenylketonurics. Women with PKU who become
pregnant must be especially careful about the phenyl alanine level in
Bridge to Genetics / Inheritance: Autosomal recessive their blood so as not to adversely affect neuorologic development in
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(AR), metabolic genetic disorder, characterized by a
the fetus. Infants born to with phenyl ketonuric mothers without
mutation in the gene for the hepatic enzyme PAH,
metabolic control during pregnency have a high risk of mental
2A
retardation, microcephaly and low birth weight.
rendering it nonfunctional.
Laboratory Diagnosis: Infants are routinely screened a
Behavioural Science / Community Medicine / Ethics: PKU Support
few days after birth for blood PA level as well as urinary Society / Genetic counseling-Prenatal Screening in Chorionic Villi
Sampling / Referral to PKU Specialty Care Centres.
phenyl pyruvic acid and phenyl acetic acids levels.

MCQ: A child with white-blond hair, blue eyes, and

pale complexion is on a special diet in which one of
the essential amino acids is severely restricted. He
has been told to avoid foods artificially sweetened
with aspartame.
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Ans: A. The child has PKU; aspartame contains
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phenylalanine. These children may be blond, blue
Dr PK_BIOGEN INNO-VISION 2015. Doc1
eyed, and pale complected because of deficient
References: Kaplan & Google.com melanin production from tyrosine.

A
Phenylalanine Tyrosine
B
Homogentisate

Valine
Maleylacetoacetate
Leucine
C
D
Methylmalonyl CoA TCA Cycle
E
F
Acetyl-CoA Glutamate
G
Alanine Pyruvate

What you have brought while coming, and what you

are going to take away while going?. The Only Thing
What You Are Going to Take Away is Karma_
Just Educate The Society_Dr P Kumar, BIO-GEN.

PHENYLKETONURIA (PKU)
Dr Kumar

Pleotropy-Abnormalities Associated with Metab Disorders

*
Ponnusamy

Dr P KUMAR_BIOGEN INNO-VISION 2015

& Dr Jegathambigai RN

Mother: The ONLY Visible GOD I Know

Acknowledgements: Lippincott, Google.com & All On-Line Resources

General Dysmorphisms (abnormality in shape or size), ODOUR.

H & N - CataCNS - Tone, seizures, tense fontanelle.
Resp - Kussmauls, tachypnea. CVS - Myocardial dysfunction.
Abdo HEPATOMEGALY. Skin Jaundice. Cataracts, retinitis pigmentosa.

Family History Helpful to Rule Out IEM.

CONSANGUINITY, ethnicity, inbreeding. Neonatal deaths, fetal losses.
Maternal family history. males - X-linked disorders. All-mitochondrial
DNA is maternally inherited. A positive family history may be helpful!.
Timing of onset of symptoms. After feeds were started?. Response
to therapies.

3
Bridge to Molecular
Biology & Genetics

Bridge to
Behavioural Science

2
Ferric ChlorideTest
Patients With PKU
Bridge to
Genetics

Bridge to ETHICS

Bridge to
Behavioural
Science
Prenatal Screening & Genetic Counselling on PKU

Prenatal Diagnosis of PKU

USMLE STEP 1 Q-1

PKU Biochemistry

Bridge to Genetics

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1. Which of the metabolites below is a

precursor of tyrosine.
A. L-Dihydroxyphenylalanine (dopa).
B. Dopamine.
C. Norepinephrine.
D. Epinephrine.
E. Phenylalanine.

Ans: E.

DIAGNOSIS

Phenylalanine Metabolism

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6

What Are The Common Signs & Symptoms of Metabolic Diseases in the Neonate?.Acute life
threatening illness. encephalopathy - lethargy, irritability, coma. Vomiting, & respiratory distress.
Seizures, Hypertonia, Hepatomegaly. Hepatic dysfunction / jaundice. Odour, Dysmorphism, failure to
thrive (FTT), Hiccoughs.
15. A new test is developed that can non-radioactively label compounds in the human body. As a physician with a back-ground In the
new field of metabolomics, you assess a 21-year-old with classical phenylketonuria (PKU). Phenylalanine is fed with a label in the phenyl
ring. In the urine, in which of the following compounds would you expect to find the greatest amount of label?.
A. Tyrosine.
B. Tryptophan.
C. Epinephrine.
D. Phenylketone.
E. Acetate. Answer: D. Phenylketonutria (PKU) is a defect in phenylalanine hydroxylase, resulting in a block in the conversion of p
Henylalanine to tyrosine. Phenylalanine accumulates in in both disorders and to converted to phenylketones. Tyrosine is the product
whose formation is blocked, and epinephrine, a product of tyrosine, would not be made or labelled. Acetate and tryptophan are very
far downstream from tyrosine.

PKU &
Neuroscience

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USMLE STEP 1 Q-2

Epidemiology

USMLE STEP 1 MCQ

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