phenylketonuria - for nursing in context to genetics

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Phenylketonuria – a biochemical
genetic disorder
Bhavesh Lakhani

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Learning Objectives
1. To conceptual autosomal recessive
transmission of PKU.
2. To be able to relate the biochemical
alteration of the affected allele
located on Chromosome 12 in PKU.

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PKU is an inborn error of metabolism that results in decreased
metabolism of the amino acid – Phenylalanine
“Inborn errors of metabolism (IEM) are disorders in which there is
a block at some point in the normal metabolic pathway''
IEMs occur due to mutations in DNA.
DNA
which code for a
Specific protein
Enzyme Receptor
Transport vehicle
Membrane pump
Structural element
CONCEPT

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Phenylketonuria:
Inherited disorder *
Affected allele :Chromosome 12q24.1
Autosomal Recessive. (1:10,000 – Europeans)
Deficiency of phenylalanine hydroxylase
CHARACTERISTICS
(Tryptophan substituted for arginine)

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Normal
Pathway of
Phenylalanine
metabolism
(Essential AA)

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Enzyme
deficient

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X
C-Decarboxylation
Phenyl
acetone
Phenyl
acetate
Phenyl
lactate
conjugated with
glutamate
Phenyl acetylglutamine
(responsible for mousy
odour of urine)
• Phenylpyruvic acid is a ketone derived of
phenylalanine .
• The Phenylpyruvic acid converted to other ketones;
phenylacetone, phenylacetyl glutamine and phenyl
lactate (phenylalanine Metabolite)
• In PKU the phenylalanine and its metabolite are
mainly excreted in urine .
Phenylalanine metabolism pathways
Phenylpyruvic acid* B-TransaminationPhenylalanin
(Ketone derivated of Ph.ala.)
A-Hydroxylation
Tyrosine

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Other commonly noted features in untreated children
include:
Microcephaly (small head),
Prominent cheek and upper jaw bones with widely
spaced teeth

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Positive Test
(Increased Result).
PKU is diagnosed and
confirmed by:
1. Greater than 4 mg/dL
serum phenylalanine.
2. Association with
low tyrosine levels of
less than 0.6 mg/dL.
3. Urinary Excretion of
phenylpyruvic acid
Diagnosis

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• Normally phenylalanine in
blood = 1- 2 mg/dl
• Normally the ratio of
phenylalanine /Tyrosine =
0.6 -1.5
• In Phenylketonuria the level of
phenylalanine in blood= 15
– 65 mg/dl, also the ratio of
phenylalanine /tyrosine may
be reach to 3 or more.
Normal level of phenylalanine

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A low-phenylalanine diet
Women with PKU can prevent birth defects by sticking to
or returning to a low-phenylalanine diet before becoming
pregnant.
Consider genetic counseling.
Is essential before pregnancy.
Prevention

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Treatment
1. No cure
2. Restrict dietary phenylalanine within 10 days of birth and dietary
supplements. Continue the diet into adulthood to have better
physical and mental health.
3. Permanent monitoring of blood phenylalanine levels
4. Oral administration of tetrahydrobiopterin (a cofactor in the
oxidation of phenylalanine) is a good potential for PKU sufferers .
5. Foods to avoid - High protein foods, such as: Meat, Fish, Poultry,
Eggs, Cheese, Milk and products, Dried beans, and peas

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HOTS
• Is phenylalanine glucogenic, ketogenic, or both?
• Tyrosine is not an essential amino acid in normal people, but it is
essential in persons with PKU – true/false?
• Patients with the disease PKU tend to have blue eyes, fair hair and
very light skin gradually developing development lags – why?
• Why is a PKU patient placed on a low phenylalanine diet instead of
a phenylalanine free diet?
• Draw the structure of asparteme. Would you let your patients take
this product – an artificial sweetener?

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Summary
• PKU is an autosomal recessive disorder caused by a deficiency
of the enzyme phenylalanine hydroxylase and a consequent
inability to metabolize phenylalanine.
• Clinical features of untreated PKU may include mental
retardation, seizures, decreased pigmentation of the skin, besides
others which can be restricting the intake of phenylalanine in the
diet.
• Female patients with PKU who discontinue dietary treatment can
give birth to children with malformations and neurologic impairment
resulting from transplacental passage of phenylalanine metabolites.

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References
• Blau N. Genetics of Phenylketonuria: Then and Now. Hum Mutat.
2016 Jun;37(6):508-15. doi: 10.1002/humu.22980. Epub 2016 Mar
18. Citation on PubMed
• Regier DS, Greene CL. Phenylalanine Hydroxylase Deficiency.
2000 Jan 10 [updated 2017 Jan 5]. In: Adam MP, Everman DB,
Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW,
Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA):
University of Washington, Seattle; 1993-2023. Available from
http://www.ncbi.nlm.nih.gov/books/NBK1504/ Citation on PubMed
• Williams RA, Mamotte CD, Burnett JR. Phenylketonuria: an inborn
error of phenylalanine metabolism. Clin Biochem Rev. 2008
Feb;29(1):31-41. PMID: 18566668; PMCID: PMC2423317.
• https://www.youtube.com/watch?v=0sauoF4ppwA
• https://www.youtube.com/watch?v=UZFOdUP4UTY
• https://www.youtube.com/watch?v=mBNRuNsDJKU

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Thank
U!!!