This document discusses phenylketonuria (PKU), a rare genetic disorder caused by mutations in the PAH gene that prevents the conversion of phenylalanine to tyrosine. This leads to a toxic buildup of phenylalanine in the body. PKU is diagnosed through newborn screening and confirmed with blood tests measuring phenylalanine levels. Treatment involves a lifelong low-phenylalanine diet to prevent intellectual disabilities and other health issues. If left untreated, PKU can cause issues such as low IQ, seizures, behavioral problems, and eczema. Early diagnosis and dietary treatment can help patients with PKU live healthy lives.

1. INBORN ERROR METABOLISM IN
PHENYLKETONURIA
BY:
HARISH K
M.SC. BIOCHEMISTRY (PURSUING)
ANNAMALAI UNIVERSITY, CHIDAMBARAM, TAMILNADU, INDIA.
THE LIFE OF BIOCHEMISTRY FORUM ORDINATOR(SOCIAL MEDIA).

2. INTRODUCTION
• INBORN ERROR IN PHENYLALANINE
AND TYROSINE
• METABOLISM.
• RARE GENETIC DISORDER
• TREATABLE DISORDER
• CANNOT USE A ANY PART OF
AMINO ACID.

3. DEFINITION:
• THE HIGH CONCENTRATIONOF PHENYLALANINEIS ACCUMULATED INTHE BLOOD IS
CALLED HYPERPHENYLALANINAEMIALEADS TO THE EXCRETION OF PHENYLALANINE IN
THE URINE THIS CONDITION IS KNOWN AS THE PHENYLKETONURIA.
• THIS CONDITION OCCURS DUE TO THE SOME ENZYME DEFICIENCY OR ABSENCE IN THE
TYROSINE METABOLISM.

5. DISCOVERY:
• IN 1934 DR.ASBJORN FOLLING ,FIRST DISCOVERY OF PHENYLKETONURIA.

6. NORMAL LEVEL IN BLOOD:
• 1-2MG %
• CLASSICAL PHENYLKETONURIA- >1200 ΜMOL / L
• MILD – 600 – 1200 ΜMOL / L
• INCIDENCE :
• 1 IN 10,000 IN INDIA .RECENT 1 IN 18,300 PER YEAR.

7. DEFECTS OF CHROMOSOME
• CLASSICAL PKU IS AN AUTOSOMAL RECESSIVE DISORDER, CAUSED BY MUTATIONS IN BOTH ALLELES
OF THE GENE FOR PHENYLALANINE HYDROXYLASE (PAH), FOUND ON CHROMOSOME 12. IN THE
BODY, PHENYLALANINE HYDROXYLASE CONVERTS THE AMINO ACID PHENYLALANINE TO TYROSINE,
ANOTHER AMINO ACID. MUTATIONS IN BOTH COPIES OF THE GENE FOR PAH MEANS THAT THE
ENZYME IS INACTIVE OR IS LESS EFFICIENT, AND THE CONCENTRATION OF PHENYLALANINE IN THE
BODY CAN BUILD UP TO TOXIC LEVELS. IN SOME CASES, MUTATIONS IN PAH WILL RESULT IN A
PHENOTYPICALLY MILD FORM OF PKU CALLED HYPERPHENYLALANEMIA. BOTH DISEASES ARE THE
RESULT OF A VARIETY OF MUTATIONS IN THE PAH LOCUS; IN THOSE CASES WHERE A PATIENT IS
HETEROZYGOUS FOR TWO MUTATIONS OF PAH (IE EACH COPY OF THE GENE HAS A DIFFERENT
MUTATION), THE MILDER MUTATION WILL PREDOMINANT.

8. GENETIC CAUSES OF PKU

9. ABNORMAL METABOLIC PATHWAYS
• THE PHENYLALANINE CANNOT CONVERTEDTO
TYROSINE.SO,THISPHENYLALANINEUNDERGOES
TRANSAMINATIONTO FORM A PHENYLPYRUVIC
ACID AND IT’S PRODUCT AS PHENYLLACTIC ACID
ARE PRODUCT.

10. UNDERSTANDING OF TYROSINE METABOLISM:

11. CLASSESS OF PHENYLKETONURIA:
• THERE ARE FIVE CLASSESSOF PHENYLKETONURIA:
1. CLASSICAL TYPE OF PHENYLKETONURIA(PKU)
2. PERISTENTHYPERPHENYLALANINAEMIA
3. TRANSIENT HYPERPHENYLALANINAEMIA
4. DIHYDROPTERINE REDUCTASE DEFICIENCY
5. ABNORMAL DIHYDROPTERINE FUNCTION.

12. CLASSESS OF PHENYLKETONURIA
Types Condition Enzyme defect Treatment
Type 1 Classical type of
phenylketonuria (PKU)
Phenylalanine hydroxylase
enzyme deficiency or absent
Low phenylalanine diet
Type 2 Persistent hyper
phenylalaninaemia
Deficiency of phenylalanine
hydroxylase enzyme
Temporary dietary therapy
Type 3 Transient mild hyper
phenylalaninaemia
Maturity is delayed on
Phenylalanine hydroxylase
enzyme
Temporary dietary therapy
Type 4 Dihydropterine reductase
deficiency
Deficiency or absence of
dihydropterine reductase
To take DOPA,5 OH
tryptophan,Carbi DOPA
Type 5 Abnormal Dihydropterine
Function
Dihydropterine synthesis
defect
To take DOPA and etc

13. SYMPTOMS:
DECREASE THE METABOLIC PRODUCT OF PHENYL ACEDIC ACID IS MINGLED WITH
GLUTAMINEIT’S RESPONSIBLEFOR MOUSY ODOUR OF URINE .
• THE PHENYLALANINE ACCUMULATEDIN THE URINE IS LEADS TO THE :
1. ODOUR OF BREATH AND SKIN
2. ECZEMA, VOMITING, IRRITABILITY.
3. FAIR SKIN AND BLUE EYE , BECAUSE, PHENYLALANINECANNOT TRANSFORM INTO
MELANIN.
4. DECREASE OR DEFECT OF SEROTONINFORMATION.
5. PSYCHIATRIC DISORDER.

14. SYMPTOMS
6. SEVERE BRAIN DAMAGE. SUCH AS MENDAL RETARDATION & SEIZURES.
7. SHAKING OR JERKING MOVEMENT IN THE ARM AND LEGS.
8. POOR DEVELOPMENT OF TOOTH ENAMEL.
9. ABNORMALITIES OFPHENOTYPE INCLUDING GROWTHFAILURE, MICROCEPHALY.
10. BEHAVIOUR CHANGE

16. DIAGNOSIS:
• NEWBORN BLOOD TESTING IDENTIFIES ALMOST ALL CASES OF PHENYLKETONURIA.
ALL 50 STATES IN THE UNITED STATES REQUIRE NEWBORNS TO BE SCREENEDFOR PKU.
MANY OTHER COUNTRIES ALSO ROUTINELY SCREEN INFANTS FOR PKU.
• IF YOU HAVE PKU OR A FAMILY HISTORY OF IT, YOUR DOCTOR MAY RECOMMEND
SCREENINGTESTS BEFORE PREGNANCYOR BIRTH. IT’S POSSIBLE TO IDENTIFY PKU
CARRIERS THROUGH A BLOOD TEST.
• ESTIMATED OF PLASMA PHENYLALANINELEVEL.
• PHENYLALANINETOLERANCETEST.
• URINE TEST (BLUE GREEN COLOR)

17. TREATMENT:
1. CONTROL THE DIETARY SUPPLEMENTS. CANNOT TAKE UP PHENYLALANINEFOODS. THAT’S LIKE.
1. EGGS
2. NUTS
3. FISH
4. BEANS
5. CHICKEN AND ETC….
2. THE UNITED STATES FOOD AND DRUG ADMINISTRATION(FDA) RECENTLY APPROVED SAPROPTERIN FOR
THE TREATMENT OF PKU. SAPROPTERIN HELPS LOWER PHENYLALANINE LEVELS. THIS MEDICATION MUST
BE USED IN COMBINATION WITH A SPECIAL PKU MEAL PLAN. HOWEVER, IT DOESN’T WORK FOR
EVERYONE WITH PKU. IT’S MOST EFFECTIVE IN CHILDREN WITH MILD CASES OF PKU.
3. PROPER NUTRITION REQUIREMENTS

19. REFERENCE:
1. CHATTARJEE IN CLINICAL BIOCHEMIS
2. HTTPS://WWW.MAYOCLINIC.ORG/ABOUT-THIS-SITE/WELCOME
3. HTTPS://WWW.NCBI.NLM.NIH.GOV/
4. MEDICALLY REVIEWED BY MELANIE SANTOS — WRITTEN BY CINDIE SLIGHTHAM ON JULY 24,
2017
5. ROBIN A WILLIAM, CYRIL DS, MAMOTLE JOHN R BURNETT