Phenylketonuria

Question 1

What type of disorder is phenylketonuria

Answer 1

Inherited metabolic disorder

Question 2

Cause of phenylketonuria

Answer 2

Absence of an enzyme

Question 3

Treatment strategy for inherited metabolic disorders

Answer 3

• supplymissingproduct
• restrictintakeofsubstrate
• increaseexcretionoftoxicproducts • replacethemissingenzyme
• replacetheabnormalgene

Question 4

What enzyme is deficient in phenylketonuria

Answer 4

Phenylalanine hydroxylase

Question 5

What type of inherited disorder is it

Answer 5

Autosomal recessive

Question 6

Incidence ratio

Answer 6

1;10,000 births

Question 7

Functions of Tyrosine

Answer 7

Used to synthesize:
• tissue proteins • melanin
• thyroxine
• catecholamines

Question 8

Clinical Features of PKU

Answer 8

• vomiting
• irritability
• poor feeding
• pale skin
• eczema
• blue eyes
• fair hair
• mental retardation

Question 9

Hyperphenylalaninaemia

Answer 9

High serum [phenylalanine] causes brain damage by:
• interfering with brain amino acid metabolism
• inhibition of neurotransmitter release

Question 10

Diagnosis of PKU

Answer 10

High serum [phenylalanine ] levels; • >700 μmol/L (normal <100 μmol/L)

Question 11

Management of PKU

Answer 11

-Restrict dietary intake of phenylalanine Ensure -adequate tyrosine intake
-Treatment should ensure following limits:

0-5 years - <360 μmol/L
5-10 years - <480 μmol/L
10+ years - <700 μmol/L

Question 12

Monitoring of PKU Treatment

Answer 12

Monitoring of treatment advisable in:
• newly diagnosed infants with PKU • pregnant females with PKU

Question 13

Difficulties with screening for inherited disease

Answer 13

• does disease have a relatively high incidence?
• can disease be detected within days of birth?
• can disease be identified by a biochemical marker which can be easily measured?
• will disease be missed clinically, and would this cause irreversible damage to the baby?
• can disease be treated and will result of screening test be available before any irreversible damage occurs to baby?
• is screening programme cost effective?

Question 14

Screening for PKU

Answer 14

Capillary blood specimen collected 6-10 days after birth:
[phenylalanine] determined by:
• Guthrie test
• thin layer chromatography
• fluorimetric method
• mass spectrometry

Question 15

Guthrie Method for PKU

Answer 15

• semiquantitativemicrobiologicalassayusing Bacillus subtilis
• sporesincorporatedintoagarmedium containing β-2-thienylalanine
• filterdiscscontainingbloodfrompatients placed on agar plate
• zonesofbacterialgrowtharounddiscfrom PKU patients

Question 16

Thin Layer Chromatography for PKU

Answer 16

Three stages for TLC:
• preparation of sample
• chromatographic separation
• identification of separated phenylalanine

Question 17

Advantages of using thin layer chromatography for pku

Answer 17

Simple
Inexpensive

Question 18

Disadvantages of using thin layer chromatography for pku

Answer 18

Semi-quantitative
Difficult to automate

Question 19

Fluorimetric Method for PKU

Answer 19

• serum proteins precipitated out before analysis
• phenylalanine reacted with ninhydrin in presence of L-
leucyl-L-alanine to give fluorescent product
• alkaline copper tartrate reagent used to stabilize fluorescent product
• fluorescent product is proportional to the [phenylalanine]
• fluorescence emitted at 515 nm is measured after excitation at 365 nm
• standards of phenylalanine used to prepare a calibration graph

Question 20

What does the enzyme do that people with pku lack

Answer 20

-converts phynylalanine(amino acid)to another amino acid called tyrosine
-the enzyme adds a oh

Question 21

role of phenylalanine

Answer 21

Used in tissue protein
Converted into tyrosine(not essential)