Inborn errors of metabolism

Nutritional Intervention for Inborn errors of metabolism

1. Mohammed S. El-Lulu
Master of Clinical Nutrition
Palestine -Gaza

2. -Inbornerrorsofmetabolismcomprisealargeclassof
geneticdiseasesinvolvingdisordersofmetabolism.
-Themajorityareduetodefectsofsinglegenesthat
codeforenzymesthatfacilitateconversionofvarious
substances(substrates)intoothers(products).
-Inmostofthedisorders,problemsarisedueto
accumulationofsubstanceswhicharetoxicor
interferewithnormalfunction,ortotheeffectsof
reducedabilitytosynthesizeessentialcompounds.
2

3. Inbornerrorsofmetabolismare
nowoftenreferredtoas
congenitalmetabolicdiseases
orinheritedmetabolicdiseases
3

4. Garrod’shypothesis
4
A BC product deficiency
substrate excess
Dtoxic metabolite

5. 5

6. Disorders of carbohydrate metabolism
•E.g., glycogen storage disease
Disorders of amino acid metabolism
•E.g., phenylketonuria , maple syrup urine disease, glutaric
acidemiatype 1
Disorders of organic acid metabolism (organic acidurias)
•E.g., alcaptonuria
Disorders of fatty acid oxidation and mitochondrial metabolism
•E.g., medium chain acyl dehydrogenase deficiency (glutaric
acidemiatype 2)
Disorders of porphyrinmetabolism
•E.g., acute intermittent porphyria
6

7. Disorders of purine or pyrimidine metabolism
•E.g., Lesch-Nyhansyndrome
Disorders of steroid metabolism
•E.g., congenital adrenal hyperplasia
Disorders of mitochondrial function
•E.g., Kearns-Sayre syndrome
Disorders of peroxisomalfunction
•E.g., Zellwegersyndrome
Lysosomalstorage disorders
•E.g., Gaucher'sdisease
7

8. 8

9. Glycogen storage disease
•Glycogenstoragedisease(GSD,alsoglycogenosis
anddextrinosis)istheresultofdefectsinthe
processingofglycogensynthesisorbreakdownwithin
muscles,liver,andothercelltypes.GSDhastwo
classesofcause:geneticandacquired.
•GeneticGSDiscausedbyanyinbornerrorof
metabolism(geneticallydefectiveenzymes)involvedin
theseprocesses.
9

10. 10

11. •Symptoms:
Hypoglycemia,Hyperlipidemia,Hepatomegaly,Lactic
acidosis,andHyperuricemia.
•Progression:Growthfailure
•Enzymedeficiency:(glucose-6-phosphatase)whichisan
enzymethathydrolyzesglucose-6-phosphateresultinginthe
creationofaphosphategroupandfreeglucose.This
deficiencyimpairstheabilityofthelivertoproducefree
glucosefromglycogenandfromgluconeogenesis.Since
thesearethetwoprincipalmetabolicmechanismsbywhich
theliversuppliesglucosetotherestofthebodyduring
periodsoffasting,itcausesseverehypoglycemia.
11

12. Treatment:
•Theessentialtreatmentgoalispreventionofhypoglycemiaandthe
secondarymetabolicderangementsbyfrequentfeedingsoffoods
highinglucoseorstarch(whichisreadilydigestedtoglucose).To
compensatefortheinabilityofthelivertoprovidesugar,thetotal
amountofdietarycarbohydrateshouldapproximatethe24-hour
glucoseproductionrate.Thedietshouldcontainapproximately65-
70%carbohydrate,10-15%protein,and20-25%fat.Atleasta
thirdofthecarbohydratesshouldbesuppliedthroughthenight,so
thatayoungchildgoesnomorethan3–4hourswithoutcarbohydrate
intake
•Twomethodshavebeenusedtoachievethisgoalinyoungchildren:
(1)continuousnocturnalgastricinfusionofglucoseorstarch;and(2)
night-timefeedingsofuncookedcornstarch.
12

13. •Isanautosomalrecessivemetabolicdisorder,whichdamages
muscleandnervecellsthroughoutthebody.Itiscausedbyan
accumulationofglycogeninthelysosomeduetodeficiencyof
thelysosomalacidalpha-glucosidaseenzymethattransforms
glycogenintoglucoseinlysosomes.
•Thebuild-upofglycogencausesprogressivemuscleweakness
(myopathy)throughoutthebodyandaffectsvariousbody
tissues,particularlyintheheart,skeletalmuscles,andweakness
facialandoralmuscles.Pompe'sdiseaseisoneoftheinfiltrative
causesofrestrictivecardiomyopathyandhepatomegaly.
•causedbyamutationinagene(acidalpha-glucosidase:also
knownasacidmaltase)onlongarmofchromosome17.
13

14. Nutrition&WeightMaintenance
•Becauseofweakenedfacialandoralmuscles,patientsofallages,
frominfantstoadults,mayexperiencedifficultieseating.Troublewith
sucking,chewing,and/orswallowingcanleadtoinsufficientcaloric
intake,problemsmaintainingahealthyweight,andageneralfailure
tothrive.Inadequatenutritionmayevenleadtoendogenousmuscle
proteinbreakdown.
Severalapproachescanaddresstheseissues:
•Physicaltherapytohelpstrengthenmusclesandallowfor
independentfeeding.
•Modificationoffoodtexturetofacilitateswallowingandreducethe
riskofaspiration.
•Carefullybalanceddietstomaximizenutrientsandprovideproteinto
muscles.
•Tubefeeding,mostcommonlyinseverelyillinfants.
14

15. Treatment:
•In2006,theEuropeanMedicinesAgency(EMEA)andtheU.S.
FoodandDrugAdministration(FDA)bothgrantedmarketing
approvalforthedrugMyozyme(alglucosidasealfa)for
treatmentofPompedisease.Myozymereplacestheenzyme
missinginthedisease,whichhelpsbreakdownglucose.
•Earlydiagnosisandearlytreatmentleadstomuchbetter
outcomes.
•Progression:Deathbyage~2years.
15

16. •Isametabolicdisorder,causedbyadeficiencyofenzyme
Myophosphorylase,whichisthemuscleisoformoftheenzyme
glycogenphosphorylase.
•Thisenzymehelpsbreakdownglycogenintoglucose-1-
phosphate,sothatitcanbeutilizedwithinthemusclecell.
•Symptoms:Theonsetofthisdiseaseisusuallynoticedin
childhood,butoftennotdiagnoseduntilthethirdorfourth
decadeoflife.Symptomsincludeexerciseintolerancewith
myalgia,earlyfatigue,painfulcramps,weaknessofexercising
musclesandmyoglobinuria.Myoglobinuria,theconditionwhere
myoglobinispresentinurine,mayresultfromseriousdamageto
themuscles,orrhabdomyolysis,whereskeletalmusclecells
breakdownrapidly,sendingtheircontentsintothebloodstream.
16

17. Treatment/Therapy
•OralvitaminB
6appearstoimpartgreaterresistanceto
fatigue.Nospecifictherapyexists,butcombinedaerobic
exerciseprogramsandhigh-proteindietsmayhelp.Some
patientslearnthelimitsoftheirexerciseandworkwithintheir
restrictions,goingontolivefairlynormallives.
•Supervisedexerciseprogramshavebeenrecommendedto
lessentherisksofextendedinactivity.
•Sucrosetreatmentisnowbeingrecommendedpriortoexercise.
•Progression:Renalfailureduetomuoglobinuria.
17

18. Vit B6 richfood High proteins food
Spinach
Redbell peppers
Garlic
Carrots
Peas
Potatoes
Milk
Egg
Fish
Liver
Meat (red)
Broccoli
Soy protein isolate
Gelatin
Egg,white
Fish meat
Milk
Chicken
Nuts
Peanut butter
Steak
Cheese
Hamburger
Broccoli
18

19. •Ismetabolicdisorderwithautosomalrecessiveinheritance
Phosphofructokinasedeficiency.
Pathophysiology:
•Inthiscondition,adeficiencyphosphofructokinaseenzyme
impairstheabilityofcellssuchaserythrocytesandskeletal
musclestousecarbohydratesforenergy.
•Themutationimpairstheabilityofphosphofructokinaseto
phosphorylatefructose-6-phosphatepriortoitscleavageinto
glyceraldehydewhichenterstheKrebscycle,effectivelylimiting
energyproduction.
•UnlikemostotherGSD,itdirectlyaffectsglycolysis.
19

20. Presentation
•Thediseasepresentswithexercise-inducedmusclecrampsand
weakness(sometimesrhabdomyolysis),myoglobinuria,aswellaswith
haemolyticanaemiacausingdarkurine.Hyperuricemiaiscommon.
Phosphofructokinasedeficiencyalsopresentsinarareinfantileform,
resultsinseveremyopathyandleadstodeathintheinfancyorearly
childhood.
Treatment/interventions
•ThereisnocureforTaruidisease,butvarioustreatmentsmay
alleviatesymptomsandcomplications.
•IndividualswithTaruidiseaseshouldbeobservanttomyoglobulinuria,
presentingasadarkdiscolorationoftheurine.Owingtotheriskof
kidneydamage,medicalhelpshouldbesoughtimmediatelyif
symptomsarise.Dialysisisneedediftoxicwasteproductsaccumulate
owingtorenalfailure(uraemia).
20

21. Treatment/interventions
•InTarui’sdisease,jaundiceismildandgenerallydoesnotrequire
treatment.
•Highuricacidconcentrationsthatmaycausegoutcanbetreatedwith
drugswhichloweruricacidlevelsintheblood.
•Theeffectivenessofdietarymanagementremainsunclear.Itis
possiblethatfoodwithahighfatcontent(notablyfattyfish)hasa
beneficialeffect,astheglycerolinneutralfatcanreplaceglucoseas
asourceofenergy.Itmaybepossibleto"teach"theskeletalmuscle
cellstooxidisefattyacidsratherthanglucosetoproduceenergy.
•IndividualswithTarui’sdiseaseshouldavoidintensivemuscleactivity
thathasmanynegativeconsequencesforphysicalandmentalhealth.
21

22. Typeof
GSD
Eponym Enzyme deficiency Progression and
Complications
GSD IIICori’s or Forbes
disease
Glycogen debrancherHypoglycemia and
myopathy
GSD IVAndersen diseaseGlycogen branching
Enzyme
Liver cirrhosis,
death at age ~5 years
GSD VIHers disease Liver glycogen
phosphorylase
Hypoglycemiaand
Hepatomegaly
GSD IX PhosphorylasekinaseDelayed motor development,
Growth retardation
GSD XIFanconi-Bickel
syndrome
Glucose transporter,
GLUT2
Hypoglycemia and
Hepatomegaly
GSDXIIRed CellAldolaseAldolaseA Exercise intolerance, and
muscle cramps
GSD XIII B-enolase Exercise intolerance, and
muscle cramps
GSD O Glycogen synthaseHypoglycemia
22

23. 23

24. •(PKU)isanautosomalrecessivemetabolicgeneticdisorder
characterizedbyadeficiencyinthehepaticenzyme
phenylalaninehydroxylase(PAH).Thisenzymeisnecessaryto
metabolizethephenylalanine(Phe)tothetyrosine.WhenPAHis
deficient,phenylalanineaccumulatesandisconvertedinto
phenylpyruvate,whichisdetectedintheurine.
•Itcancauseproblemswithbraindevelopment,leadingto
progressivementalretardation,braindamage,andseizures.
•Optimaltreatmentinvolvesloweringblood(Phe)levelstoasafe
rangeandmonitoringdietandcognitivedevelopment.
•PKUisnormallydetectedusingtheHPLCtestafterbirth.
24

25. SignsandSymptoms:
•thediseasemaypresentclinicallywithseizures,albinism(excessively
fairhairandskin),anda"mustyodor"tothebaby'ssweatandurine
(duetophenylacetate,oneoftheketonesproduced).
•Treatment:bymanagingandcontrolling(Phe)levelsthroughdiet,or
acombinationofdietandmedication.
•AllPKUpatientsmustadheretoaspecialdietlowinphenylalanine
foratleastthefirst16yearsoftheirlives.Thisrequiresseverely
restrictingoreliminatingfoodshighinphenylalanine,suchasmeat,
chicken,fish,eggs,nuts,cheese,legumes,cowmilkandotherdairy
products.Starchyfoodssuchaspotatoes,bread,pasta,andcorn
mustbemonitored.
•Infantsrequireacommercialformulaofmilkthatfreefrom(Phe).
25

26. •Tyrosine,whichisnormallyderivedfromphenylalanine,mustbe
supplemented.
•Thesweetenerofaspartamemustbeavoided,asaspartame
consistsoftwoaminoacids:phenylalanineandasparticacid.
•Theoraladministrationoftetrahydrobiopterin(orBH4)(a
cofactorfortheoxidationofphenylalanine)canreduceblood
levelsofthisaminoacidincertainpatients.
•Forchildhood,wecanaddsomefruitsandvegetablesthelow
in(Phe)whichprovideessentialvitaminsandminerals.
26

27. 27

28. •Alsocalledbranched-chainketoaciduria,isanautosomalrecessive
metabolicdisorderaffectingbranched-chainaminoacids.Itisone
typeoforganicacidemia.
•MSUDiscausedbyadeficiencyofthebranched-chainalpha-keto
aciddehydrogenasecomplex(BCKDH),leadingtoabuildupofthe
branched-chainaminoacids(leucine,isoleucine,andvaline)andtheir
toxicby-productsinthebloodandurine.
•Thediseaseischaracterizedinaninfantbythepresenceofsweet-
smellingurine,withanodorsimilartothatofmaplesyrup.Infants
withthisdiseaseseemhealthyatbirthbutifleftuntreatedsuffer
severebraindamageandeventuallydie.
•Fromearlyinfancy,symptomsoftheconditionincludepoorfeeding,
vomiting,dehydration,lethargy,seizures,hypoglycaemia,
ketoacidosis,pancreatitis,comaandneurologicaldecline.
28

29. Management:
•KeepingMSUDundercontrolrequirescarefulmonitoringof
bloodchemistryandinvolvesbothaspecialdietandfrequent
testing.
•Adietwithminimallevelsoftheaminoacidsleucine,isoleucine,
andvalinemustbemaintainedinordertopreventneurological
damage.Asthesethreeaminoacidsarerequiredforproper
metabolicfunctioninallpeople,specializedprotein
preparationscontainingsubstitutesandadjustedlevelsofthe
aminoacidshavebeensynthesizedandtested,allowingMSUD
patientstomeetnormalnutritionalrequirementswithoutcausing
harm.
29

30. Leucine(Food) Isoleucine (Food)Valine(Food)
Soybeans
Lentils
Cowpea ايبوللا
Beef (lean and trimmed)
Peanuts
Salmon fish
Shrimp
Nuts
Eggs
Eggs
Soy protein
Seeweed
Milk
Cheese
Sesame seeds
Sunflower seeds
Cod liver
Closed to Isoleucine sources
30

31. •Glutaricacidemiatype1(or"GlutaricAciduria","GA1",or
"GAT1")isaninheriteddisorderinwhichthebodyisunableto
breakdowncompletelytheaminoacidslysine,hydroxylysine
andtryptophan.Excessivelevelsoftheirintermediate
breakdownproducts(glutaricacid,glutaryl-CoA,3-
hydroxyglutaricacid,glutaconicacid)canaccumulateand
causedamagetothebrain(andalsootherorgans),but
particularlythebasalganglia,whichareregionsthathelp
regulatemovement.GA1causessecondarycarnitinedeficiency,
asglutaricacid,likeotherorganicacids,isdetoxifiedby
carnitine.Mentalretardationmayalsooccur.
31

32. •CorrectionofsecondaryCarnitinedepletionbyoral
supplementation.
•Precursorrestriction:Dietarycontrolmayhelplimitprogression
oftheneurologicaldamage.
•Theentryoftryptophantothebrainiscrucialintheproper
synthesisoftheneurotransmitterserotonininthebrain…..…..
5-hydroxytryptophan.
•Theprecursorofserotoninthatisnotmetabolizedtoglutaryl-
CoA,glutaricacidandsecondarymetabolites,couldbeusedas
anadjuncttoselectivetryptophanrestriction.
32

33. 33

34. 34

35. •Alkaptonuria(blackurinedisease)isarareinheritedgenetic
disorderofphenylalanineandtyrosinemetabolism.Thisisan
autosomalrecessiveconditionthatisduetoadefectinthe
enzymehomogentisate1,2-dioxygenase,whichparticipatesin
thedegradationoftyrosine.
•Asaresult,atoxictyrosinebyproductcalledhomogentisicacid
(oralkapton)accumulatesinthebloodandisexcretedinurine
inlargeamounts.Excessivehomogentisicacidcausesdamageto
cartilage(leadingtoosteoarthritis)andheartvalvesaswellas
precipitatingaskidneystones.
35

36. •Notreatmentmodalityhasbeendemonstratedtoreducethe
complicationsofalkaptonuria.
•Commonlyrecommendedtreatmentsincludedietaryrestriction
ofphenylalanineandtyrosineandlargedosesofascorbicacid
(vitaminC).
•Dietaryrestrictionmaybeeffectiveinchildren,butbenefitsin
adultshavenotbeendemonstrated.
36

37. 37

38. •Medium-chainacyl-coenzymeAdehydrogenasedeficiency
(MCADD)isafattyacidoxidationdisorderassociatedwith
inbornerrorsofmetabolism.Itisduetodefectsintheenzyme
complexknownasmedium-chainacyldehydrogenase(MCAD)
andreducedactivityofthiscomplex.Thiscomplexoxidizes
mediumchainfattyacids(Fattyacidshaving6-12carbons)
whilereducingFADtoFADH
2.
•Itisrecognizedasoneofthemorerarecausesofsuddeninfant
deathsyndrome(SIDS).
38

39. Treatment:
•ThereisnocureforMCADD,butoncediagnosed,adverseeffectscan
bepreventedbypropermanagement.
•Themostimportantpartoftreatmentistoensurethatpatientsnever
gowithoutfoodforlongerthan10–12hours(overnightfast).
•Patientswithanillnesscausinglossofappetiteorseverevomiting
mayneedIVglucosetomakesurethatthebodyisnotdependenton
fattyacidsforenergy.Patientsalsousuallyadheretoalow-fatdiet.
•Patientsmayalsotakedailydosesofcarnitine,whichhelpsreduce
toxicaccumulationoffattyacidsbyformingacylcarnitines,whichare
excretedintheurine.
•Severityofsymptomsseemstodecreaseafterpuberty.
39

40. 40

41. •Acuteintermittentporphyria(AIP)isarareautosomal
dominantmetabolicdisorderaffectingtheproductionofheme,
theoxygen-bindingprostheticgroupofhemoglobin.Itis
characterizedbyadeficiencyoftheenzymeporphobilinogen
deaminase.
•SymptomsofAIPincludeabdominalpain,constipation,muscle
weakness,andalsotendtodevelopvariouspsychiatricillnesses.
•Treatment:Ahigh-carbohydrateaglucose10%infusionis
recommended,whichmayaidinrecovery.
•Ironintakeshouldbeadequatetoavoidirondeficiency.
41

42. 42

43. 43

44. •Isinherited(X-linkedrecessive)disordercausedbyadeficiency
ofthehypoxanthine-guaninephosphoribosyltransferase
enzyme(HGPRT),producedbymutationsintheHPRTgene.
•TheHGPRTdeficiencycausesabuild-upofuricacidinallbody
fluids.Thisresultsinbothhyperuricemiaandhyperuricosuria,
associatedwith:
1-Severegoutandkidneyproblems,
2-Neurologicalsignsincludepoormusclecontrol,
3-Moderatementalretardation.
•Thesecomplicationsusuallyappearinthefirstyearoflife.
44

45. •Inthesecondyearoflife,aparticularlystrikingfeatureofLNS
isself-mutilatingbehaviors,characterizedbylipandfinger
biting.
•TheLNSshouldassociatedwithteethextractionandrestrainsto
avoidself-mutilatingbehaviors.
Treatment:
•Theelevatedlevelofuricacidinbloodandurinedoesn’trelate
tohighpurinediet,butduetophysiologicalerror.
•BecausealackofHGPRTcausesthebodytopoorlyutilize
vitaminB
12,someboysmaydevelopmegaloblasticanemiaand
neurologicalsymptoms.
45

46. 46

47. •Congenitaladrenalhyperplasia(CAH)referstoanyofseveral
autosomalrecessivediseasesresultingfrommutationsofgenes
forenzymesmediatingthebiochemicalstepsofproductionof
cortisolfromcholesterolbytheadrenalglands
(steroidogenesis).
•Mostoftheseconditionsinvolveexcessiveordeficient
productionofsexsteroidsandcanalterdevelopmentof
primaryorsecondarysexcharacteristicsinsomeaffected
infants,children,oradults.Approximately95%ofcasesofCAH
aredueto21-hydroxylasedeficiency.
•Steroid21-hydroxylaseisoneofacytochromeP450enzymes
thatisinvolvedwiththebiosynthesisofthesteroidhormones
aldosteroneandcortisol.
47

48. Treatment:
•Supplyingenoughglucocorticoidtoreducehyperplasiaand
overproductionofandrogensormineralocorticoids.
•Providingreplacementmineralocorticoidandextrasalt.
•Providingreplacementtestosteroneorestrogenatpuberty.
Diet:
•Patientswithcongenitaladrenalhyperplasiashouldbeonan
unrestricteddiet.
•Patientsshouldhaveampleaccesstosaltbecausesaltwasting.
•Infantswhohavesaltwastinggenerallybenefitfromsupplementation
withNaCl(2-4g/d)addedtotheirformula.
•Caloricintakemayneedtobemonitoredandrestrictedifexcess
weightgainoccursbecauseglucocorticoidsstimulateappetite.
Activity:restrictionisnotnecessaryifappropriateglucocorticoid.
48

49. 49

50. •(KSS)isamitochondrialmyopathywithatypicalonsetbefore
20yearsofage.
•KSSisamoreseveresyndromicvariantofchronicprogressive
externalophthalmoplegia(CPEO),asyndromethatis
characterizedbyisolatedinvolvementofthemusclescontrolling
eyelidmovementandthosecontrollingeyemovement(extra-
ocularmuscles).Thisresultsinptosis(droppinguppereyelid)
andophthalmoplegiarespectively.
•KSSinvolvescardiacconductionabnormalities.
•Otherareasofinvolvementcanincludecerebellarataxia,
deafness,diabetesmellitus,growthhormonedeficiency,
hypoparathyroidism,orotherendocrinopathies.
50

51. Chronic progressive external
ophthalmoplegia
Eyelid ptosis
51

52. •Treatment:CurrentlythereisnocurativetreatmentforKSS.
•OnestudydescribedapatientwithKSSwhohadreducedserum
levelsofcoenzymeQ10.Administrationof60–120mgofCoenzyme
Q10for3monthsresultedinnormalizationoflactateandpyruvate
levels,improvementofpreviouslydiagnosedfirstdegreeAVblock,
andimprovementofocularmovements**.
FoodsrichinCoQ10:beefliver,sesame&cottonseedoil,sardines,
eggs,garlicandsweetpotatoes.
•Screeningforendocrinologicdisordersshouldbeperformed,
includingmeasuringserumglucoselevels,thyroidfunctiontests,
calciumandmagnesiumlevels,andserumelectrolytelevels.
**Ogasahara,Setal.(1985)"Improvementofabnormalpyruvatemetabolismandcardiacconductiondefectwith
coenzymeQ(10)inKearns-Sayresyndrome."Neurology35:372-377.PubMedID:3974895
52

53. 53

54. •Zellwegersyndrome,alsocalledcerebrohepatorenalsyndromeisa
rare,congenitaldisorder(presentatbirth),characterizedbythe
reductionorabsenceofperoxisomesinthecellsoftheliver,kidneys,
andbrain.
•Peroxisomescontainoxidativeenzymes,suchascatalase,D-amino
acidoxidase,anduricacidoxidase.
•Itischaracterizedbyanindividual'sinabilitytobeta-oxidizevery-
longchainfattyacidsintheperoxisomesofthecell.
Themostfeaturesinclude
1-Anenlargedliver,highlevelsofironandcopperinthebloodstream,
andvisiondisturbances.
2-Symptomsatbirthmayincludealackofmuscletone,andglaucoma.
3-Mentalretardation,andaninabilitytosuckand/orswallow.
4-Jaundiceandgastrointestinalbleedingmayalsooccur.
54

55. •Treatment:
•TreatmentofZellwegersyndromeisprimarilysymptomaticand
supportive.
•VitaminKmaybeneededtoavoidabnormalbleeding.
•DHAisanessentialfattyacid,whichisdeficientinpatientswith
Zellwegersyndrome.Improvementhasbeenreportedinsome
patients.
•Actually;thereisnocureforZellwegersyndromeandpatient
willdieatfirstyearoflife.
55

56. 56

57. •Gaucher'sdiseaseisageneticdiseaseinwhichafattysubstance
accumulatesincellsandcertainorgans.
•Itiscausedbyahereditarydeficiencyoftheenzyme
glucocerebrosidase.Theenzymeactsonafattysubstance
glucocerebroside(alsoknownasglucosylceramide).
•Whentheenzymeisdefective,glucocerebrosideaccumulates,
particularlyinwhitebloodcells(mono&lymphocyte).
•Glucocerebrosidecancollectinthespleen,liver,kidneys,lungs,brain
andbonemarrow.
SignandSymptoms:
•Painlesshepatomegaly,splenomegaly,mentalretardation,andrapid
andprematuredestructionofbloodcells,leadingtoanemia.
57

58. Treatment:
•Theenzymereplacementtherapyisessentialforthetreatment.
•OsteoporosiscanbereducedbyVitD.
•Gaucherpatientshaveincreasedcaloricrequirementsbecause
theyhavehigher-than-normalmetabolism.
•Despitetheneedformorefood,patientswithpronouncedliver
and/orspleenenlargementcanfrequentlyhaveasuppressed
appetite.Theenlargedorgansleavelittleroominthebody
cavityforafullstomach,sopatientsoftenreportasensationof
feelingfull,evenafterhavingonlyafewbitesoffood.
•MineralsorvitaminsspeciallyB12arerecommended..
58

59. Part-II

60. •Galactosemiaisaninheriteddisordercharacterizedby
aninabilityofthebodytoutilizegalactose.
•Galactosemiameans"galactoseintheblood".
•Themainsourceofgalactoseinthedietismilkproducts.
•Thedeficientenzymethatisresponsibleofgalactosemia
iscalledgalactose-1-phosphateuridyltransferase
(GALT).TheGALTenzymeenablesthebodytobreak
downgalactoseintoglucoseforenergy.
•Galactosemiaistreatedbyremovingfoodsthatcontain
galactosefromthediet.Untreatedgalactosemiawill
resultinaharmfulbuild-upofgalactoseandgalactose-1-
phosphateinthebloodstreamandbodytissues.
60

61. •Infantswithunrecognizedgalactosemiausuallyhave
problemswithfeedinganddonotgrowastheyshould.
•Ifgalactosemiaisnottreated,infantscandevelop
cataracts,liverdisease,kidneyproblems,braindamage,
andinsomecases,canleadtodeath.
Diet:
•Thedietshouldallowmostprotein-containingfoodsother
thanmilkandmilkproducts.
•Lactoseisoftenusedasafillerorinactiveingredientin
medicines,andmightnotbelistedonthepackage.
61

62. Somefoodscontaingalactoseandareunacceptable:
•Sherbet:Traditionalcolddrinkpreparedofspeciesofcherries,
rose,licoriceorHibiscuswithdiaryproducts.
62
Butter Buttermilk and solids
Calcium caseinate Casein
Nonfat milk Cream
Dry milk and milk protein beans
Hydrolyzed protein made from casein Ice cream
Lactalbumin(milk albuminate) Lactose
Milk and milk solids Milk chocolate
Nonfat dry milk & solids Cheese
Organ meats (liver, heart, etc.) Sherbet
Sodium caseinate Sour cream
Whey نبللا لصمand whey solids Yogurt

63. •Foodswithmorethan10mgGalactose/100gramoffood:
•Foodswith5-10mgGalactose/100gramoffood:
•Apricot, Avocado, Cabbage, Cantaloupe, Cauliflower, Celery, Sweet corn,
Cucumber, Eggplant, Green grapes, Grapefruit, Kale, Lettuce, Oranges,
Peas, White potato, RadishSpinach, Turnip ,Apple ,Banana ,BroccoliCarrot,
Kiwi, Green onion, Yellow onion, Pears, Sweet potato, Pumpkin.
63
Tomato 23
Date 11
Papaya 29
Bell Pepper 10
Watermelon 15

64. •Isafructosepoisoningisahereditaryconditioncausedbya
deficiencyofliverenzymesthatmetabolisefructose.
•DeficiencyofFructose1-PhosphateAldolaseorAldolaseB
enzymewhichleadtoaccumulateFructose-1-phosphatein
blood.
•Aldolase-B,convertsF-1-phtoDihydroxyacetonephosphate
andglyceraldehyde.(ActsinGlycolysisandGluconeogenesis).
•Exclusivebreastfeedingbabyremainwithoutsymptoms.
•Symptomsincludevomiting,hypoglycemia,failuretothrive,
cachexia,hepatomegaly,jaundice,coagulopathy,coma,and
severemetabolicacidosis(duetolacticacidosis).
Treatment:fructoseandsucrosefreediets.
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65. Avoid foods that contain: Fruits And Fruit Juices:
•Fructose
•High-fructose corn syrup
•Table sugar (sucrose)
•Confectioner's sugar or powdered
sugar
•Fruit and fruit juices
•Honey
•Regular sodas
•Flavored water
•Sorbitol
•Sports drinks
•Sweetened milk or sweetened milk
beverages
•Molasses
Dates -32 grams
Figs -29.6 grams
Dried peaches -13.5 grams
Dried apricots -12.5 grams
Grapes -8 grams
Pears -6.2 grams
Apples -6 grams
Apple juice -5.6 grams
Mango -5.5 grams
Cherries -5.3 grams
Bananas -4.85 grams
Kiwi Fruit -4.3 grams
Watermelon -3.35 grams
Orange Juice -2.7
Strawberries -2.4 grams
Oranges -2.2 grams
Pineapple -2.0 grams
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66. •Isadisordercharacterizedbythepresenceofahigherlevelof
methemoglobinintheblood.
•Methemoglobinisanoxidizedformofhemoglobin,{theironwithin
hemoglobinisoxidizedfromtheferrous(Fe
2+
)statetotheferric
(Fe
3+
)state},thathasnoaffinityforoxygen,resultinginnooxygen
deliverytothetissue,sohypoxiacanoccur.
•Clinically,thisconditioncausescyanosis.
•Themajorcauseofinbornisglucose-6-phosphatedehydrogenase
[G6PD]deficiencyandcytochromeb5oxidasedeficiency)orsevere
acidosis,whichimpairsthefunctionofcytochromeb5oxidase.
•Thisisparticularlyevidentinyounginfantswithdiarrhea,inwhom
excessivestoolbicarbonatelossleadstometabolicacidosis.
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67. •Ascorbicacidisanantioxidantthatmayalsobeadministeredin
patientswithmethemoglobinlevelsofmorethan30%.
•Oralascorbicacid(200-500mg)hasbeenfoundtobe
partiallyeffective,someauthorsrecommendusinghigherdoses
ofupto1000mg/d.
•Somevegetables(beetsرجنبلا ,spinach,andcarrots)arehighin
nitritecontent,mayneedtobeavoidedinsusceptiblepatients
aswellascontaminatedwaterofnitratesandnitrites.
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Food Sources of Vit C
(adapted from world healthiest food; WHFood’s)
Food Serving size Calories Vit-C (mg)
Bell peppers, red, raw, slices 1 cup 24.8 174.8
Broccoli,steamed 1 cup 43.7 123.4
Strawberries 1 cup 43.2 81.70
Lemon juice, fresh ¼ cup 15.3 28.06
Grapefruit ½each 36.9 46.86
Kiwifruit 1 each 46.4 57.00
Cantaloupe 1 cup 56.0 67.52
Oranges 1 each 61.6 69.70
Tomato, ripe 1 cup 37.8 34.38
Banana 1 each 108.1 10.75
Apples 1 each 81.4 7.87
Grapes 1 cup 61.6 3.68
Avocado,slices 1 cup 235 11.53

69. •CeliacDisease(CD)isalifelonginheritedautoimmune
conditionaffectingchildrenandadults.
•WhenpeoplewithCDeatfoodsthatcontaingluten,itcreates
animmune-mediatedtoxicreactionthatcausesdamagetothe
smallintestineanddoesnotallowfoodtobeproperly
absorbed.(Forchildren,growthfailureisthebiggestchallenge)
•EvensmallamountsofgluteninfoodscanaffectthosewithCD
andcausehealthproblems.
•Damageoccurtosmallbowelevenwhennosymptomspresent.
•Glutencanfindinwheat,barley,andrye.
•SensitivityofglutenistoGliadinportionofprotein.
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71. Gluten freediet (Accepted) Have Gluten (Not-Accepted)
•Freshmeats,fishandpoultry
•Mostdairyproducts(duetoLactase
deficiency,milkmayberestricted)
•Fruits
•Vegetables
•Rice
•Potatoes
•Gluten-freeflours(soy,corn)
•Breads (bran, germ, & semolina)
•Cereals
•Crackers
•Pasta
•Cookies
•Cakes and pies
•Sauces
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Reading food labels is important.
Actually, Notreatment for celiac disease.
Q: What’s about Oats?

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