metabolic disorders pdf.pdf inborn errors

inborn errors

2. Inborn errors of metabolism
Inbornerrorsofmetabolismareraregenetic
(inherited)disordersinwhichthebodycannot
properlyturnfoodintoenergy.Thedisordersare
usuallycausedbydefectsinspecificproteins
(enzymes)thathelpbreakdown(metabolize)
partsoffood.

3. PHENYLKETONURIA (PKU)
Phenylketonuria(PKU)isaninbornerrorof
metabolismthatresultsindecreased
metabolismoftheaminoacidphenylalanine
Itisduetothedefetctofenzymephenylalanine
hydroxylasethatbreaksdownphenylalanine.

5. Complications
Ifitisn'ttreated,damagetothebrainand
nervoussystemcanleadto:
1.Learningdisabilities
2.Behaviouraldifficulties
3.Epilepsy

6. Prevention
Follow a low-phenylalanine diet
Women with PKU can prevent birth defects by sticking
to or returning to a low-phenylalanine diet before
pregnancy.
Consider genetic counseling.
If you have PKU, a close relative with PKU or a child with
PKU, you may also benefit from genetic counseling
before becoming pregnant.

7. Diagnosis

8. Treatment
Oraladministrationoftetrahydrobioptrin(a
cofactorintheoxidationofphenylalanine)canbe
administered.
Foodstoavoid-Highproteinfoods,suchas:
Meat,Fish,Poultry,Eggs,Cheese,Milkand
products,Driedbeans,andpeas

9. Health Education
Permanentmonitoringofbloodphenylalaninelevels
Astrictlycontrolledphenylalaninefreedietuptothe
ageofabout14yearsold.
Phenylketonuria(PKU)canbesuccessfullytreated
withalow-proteindietanddietarysupplements
Thedietmustbestrictlyfollowed
Thosewhocontinuethedietintoadulthoodhave
betterphysicalandmentalhealth.

10. GALACTOSEMIA
Milkanddairyproductscontainlactose,themajor
dietarysourceofgalactose.
Themetabolismofgalactoseproducesfuelfor
cellularmetabolismthroughitsconversionto
glucose-1-phosphate.
Galactosealsoplaysanimportantroleinthe
formationofgalactosides,whichinclude
glycoproteins, glycolipids, and
glycosaminoglycans.

11. Galactosemiadenotestheelevatedlevelof
galactoseinthebloodandisfoundin3distinct
inbornerrorsofgalactosemetabolismin1ofthe
followingenzymes:
Galactose-1-phosphateuridyltransferase,
Galactokinase,
Uridinediphosphategalactose-4-epimerase.

12. Deficiency of galactose-1-phosphate
uridyltransferase(GALT)resultsinaccumulation
ofgalactose-1-phosphateandmetabolites(e.g.
galactitol)thatmighthavetoxiceffectontheliver
andotherorgans.

13. Definition
Itisarareautosomalrecessivedefect,dueto
absenceoftheenzyme,galactose-1-
phosphate-uridyletransferasewhichis
responsibleforconvertinggalactoseto
glucose.

14. Causes
1.Genetic causes,(genetic mutation, and family
history).
2.Accumulation of galactose.
3.Reduction to galactitol.

15. Signs and Symptoms

16. Types
There are3 forms of this disorder.
1. Classic galactosemia
2. Galactokinasedeficiency
3. Deficiency of uridyldiphosgalactose-4 epimerase
deficiency

17. Classic Galactosemia:
Itresultsfromdeficiencyofgalactose-1phosphate
uridyltransferase.
Theabsenceofthisenzymeresultsin
accumulationofgalactose-1-phosphate,itcauses
injurytothekidney,liverandbrain.

18. Clinical manifestations ofClassic
galactosemia:
Inthenewborn:jaundice,hepatomegaly,
vomiting,hypoglycaemia,convulsions,lethargy,
andirritability,feedingdifficulties,poorweight
gain,cataract,hepaticcirrhosis,ascites,
splenomegalyandmentalretardation.
Gram-negativesepsis,especiallywithE.coliis
common.

19. Diagnosis
Urinesamplescollectedwhilethepatientis
receivingmilk.Urinecanbeidentifiedasgalactose
bychromatographyorbyenzymatictestspecific
forgalactose.
Finalconfirmationofdiagnosisismadeby
estimatingtransferaseenzymesinerythrocytes.

20. Treatment
Thetreatmentconsistsoftotaleliminationof
galactosefromthediet(milkandmilkproducts)
rightfrombirthtoavoidliverinjury,mental
retardation,cataractandrecurrenthypoglycaemia.

21. GalactokinaseDeficiency:
Thisdisorderresultsfromabsenceofgalactokinase
thatcatalyzestheinitialphosphorylationof
galactoseandisclinicallycharacterizedby
galactosemia,galactosuriaandcataractwithout
mentalretardationoraminoaciduria.
Definitivediagnosis:testdonefordeficiencyof
galactokinaseactivityinerythrocytes.

22. Deficiency Of
UridylDiphosgalactose-4
EpimeraseDeficiency:
Thisdisordermaybebenignorlikeclassical
galactosemiadependingonthetypeof
disorder.
Treatment:Galactosefreediet..

23. Diagnosis Evaluation
Infantsaffectedbygalactosemiatypicallypresent
withsymptomsoflethargy,vomiting,diarrhea,
failuretothriveandjaundice.
Newbornscreening:amniocentesisorfromthe
placenta(chorionicvillussamplingorCVS).
Galactosemiatest:Itisabloodtestorurinetest
thatchecksforthreeenzymes.

24. Management
Theonlytreatmentforclassicgalactosemiais
eliminatinglactoseandgalactosefromthediet.
Infantswithclassicgalactosemiacannotbebreast-
fedduetolactoseinhumanbreastmilkandare
usuallyfedasoya-basedformula.
Foodslikebutter,non-fatmilk,buttermilk,Cream,
milkChocolate,soySaucearenotacceptableinthe
dietforgalactosemia.

26. Complications
1.Speech deficits.
2.Ataxia.
3.Dysmetria.
4.Diminished bone density.
5.Cataract.