Вы находитесь на странице: 1из 5

b nered|tary d|sorders of the metabo||sm of sugars and fats

Metabo||sm of sugars

Inborn errors of metabo||sm of ga|actose
CalacLosemla (galacLose lncrease ln serum) can be caused by defecLs ln Lhese L galacLose1phosphaLeurldylLransferzy
urldyldlfosfLgalakLosa4eplmerzy galacLoklnase
C|ass|c galacLosemla
A8 serlous lllness lncldence of 1 30 000
Cause lack of Ga|1ur|dy|transferzy meLabollzes Cal1
aLhogenesls Cal1 accumulaLes ln Lhe llver kldneys and braln eye lens
alLernaLlve rouLe ls meLabollsed Lo galacLlLol whlch ls Loxlc
Cllnlcal plcLure sympLoms begln beLween 4 and 9dnem
Vom|t|ng hepatomega|y progress|ve [aund|ce |ethargy or se|zures
8emlnlscenL of acuLe sepLlc dlsease wlLh hepaLlc and renal fallure
uevelops ln unLreaLed cerebral edema ofLen bllaLeral caLaracL
lor nnP Lhe sympLoms appear only afLer Lransferrlng Lo Lhe mllk dleL
ulagnosls deLecLlon of lncreased concenLraLlons of urlnary galacLlLol and gal1 ln Lhe era
ls always necessary Lo conflrm Lhe enzymaLlc and molecular level
1herapy when Lhey hear Lhe suspecL |mmed|ate|y d|scont|nu|ng m||k d|et
When Lhe dlagnosls ls lndlcaLed bezlakLzov llfelong dleL
rognosls may noL be favorable aL Lhe Llme nor recognlzed because Lhe chlld has been exposed Lo galacLose lnLrauLerlne
MosL ofLen arlse speech dlsorder and Lhe emergence of glrls hypergonadoLrofnlho hypogonadlsm

Inborn errors of metabo||sm of fructose

nered|tary fructose |nto|erance
A8 serlous dlsease Lhe lncldence of 140 000
L lacks frucLose6 ln llver aldolasa
lrucLose6 accumulaLes ln Lhe llver and cause compeLlLlve lnhlblLlon of phosphorylase
and prevenLs spllLLlng of glycogen lnLo glucose whlch causes severe hypoglycemla
Cllnlcal slgns appear shorLly afLer Lhe lnfanLs began Lo be glven sugar
SympLoms are vlrLually ldenLlcal wlLh classlcal galacLosaemla [usL mlsslng caLaracL
1olerance LesL frucLose kl could resulL ln severe hypoglycaemla shock and deaLh
ulagnosls deLecLlon muLaLlon A149 aldolase 8 gene
1reaLmenL CompleLe e||m|nat|on of fructose from the d|et
Lven when Lhe prognosls ls uncerLaln adherence Lo dleL

8en|gn fruktosur|e
ueflclL frukLoklnzy
lrucLose absorbed ln Lhe lnLesLlne can be no organlsm used meLabollcally and excreLed ln Lhe urlne wlLhouL cllnlcal sympLoms

Inborn errors of metabo||sm of g|ycogen g|ycogen storage
Are due Lo meLabollc dlsorders LhaL resulL ln elLher abnormal sLrucLure or abnormal glycogen conLenL ln Llssues
Clycogen sLorage dlsease Lype 0
Aglykogenza lack glykogensynLeLasy enzyme ln Lhe llver (noL muscle leukocyLes and enLerocyLes)
Llver glycogen ls reduced below 2 normal
Cllnlcal plcLure sLocks wlLh severe hypoglycemla cramps lead Lo braln damage and menLal reLardaLlon
Cccur malnly ln Lhe mornlng afLer overnlghL fasLlng are accompanled by keLonemla
Clucose observed afLer prolonged hyperglycemla and lncreased serum lacLaLe (llver glycogen does noL Lhey do lL lacLaLe)
urgenL dlagnosls ls essenLlal Lo Lhe survlval of Lhe chlld eplsodes of hypoglycemla can be prevenLed by frequenL admlnlsLraLlon of foods
rlch ln proLeln

G|ycogen storage d|sease type Ia
von G|ereks dlsease hepaLorenal glycogenosls
uefecL ln glucose6phosphaLase (glc6 converLs Lo CLC) Lhe A8 gene ls 17chr
Cllnlcal plcLure sLarLlng ln lnfancy progresslve hepaLomegaly and fasLlng hypoglycaemlc convulslons
uurlng febrlle condlLlons are more frequenL hypoglycemla and lacLlc acldosls ls accompanled wlLh breaLhlng kussmaulovym
CharacLerlsLlc facles uoll lace dolls face
1he body adapLs Lo hypoglycemla lnsulln secreLlon decreases lL acLlvaLes llpase ln adlpose Llssue occurs hyperllpoproLelnemla
lncreased Lhelr breaklng down formed keLone bodles whlch LogeLher wlLh lacLaLe acldosls conLrlbuLe Lo
Clucagon does noL lncrease glucose buL lacLaLe
Slowlng growLh and puberLy ls behlnd schedule
ln adulLhood may occur xanLhomas renal fallure wlLh hyperLenslon and gouL llver adenomas
LaboraLory fasLlng hypoglycemla (frequenL only ln lnfanLs and Loddlers)
PyperlacLaLemla and hyperllpldemla whlch blocks Lhe excreLlon of urlc acld and hyperurlcemla makes
Sono nefromegalle and hepaLomegaly llver adenomas can be
Llver blopsy Worn sLeaLosls and glycogen
1herapy Lhe alm ls Lo prevenL sLaLes of severe hypoglycemla and Mac
uleL Lherapy frequenL use of dleL wlLh resLrlcLlon of anlmal faL lacLose sucrose and frucLose
We pay Lhe calorlc needs mosLly sLarches and malLodexLrlns
lrom Loddler age are served afLer every meal corn sLarch
1he nlghL ls sulLable conLlnuous nasogasLrlc Lube feedlng and Lo 30 of dally lncome broughL ln Lhe nlghL
AcuLe meLabollc dlsrupLlon assoclaLed wlLh lacLlc acldosls durlng lnfecLlon musL be admlnlsLered lnglucose
rognosls ln chlldhood ls good ln adulLs aL rlsk of developlng hepaLlc renal and cardlovascular compllcaLlons

G|ycogen Storage D|sease 1ype Ib
1ransporL defecL CLC6
ls cllnlcally lndlsLlngulshable from la buL frequenL neuLropenla and consequenLly aphLhous sLomaLlLls and ulceraLlon of Lhe lnLesLlnes

G|ycogen Storage D|sease 1ype II
ompe d|sease generallzed glycogenosls
Pas Lwo forms lla affecLs lnfanLs (enzymopaLhles) llb older chlldren and adulLs (enzymopenle)
1he fallure of lysosomes of llver muscle and hearL Lhey accumulaLe glycogen
Clycogen accumulaLes ln Lhe cyLoplasm of Lhe muscle (lncludlng myocardlum)
renaLal dlagnosls perhaps flndlng abnormal lysosomes ln amnlocyLes
A classlcal form of dlsease ls always faLal lL ls Lhe slze afLer blrLh hearL border
uurlng Lhe weeks and monLhs Lo become fully hypoLonlc weak sucklng breaLhlng superflclally
ronounced cardlomegaly LCC aL hlgh C and shorLened gear fallure
SllghLly enlarged llver
Consclousness ls noL vlolaLed nor lnLellecL
lrequenL asplraLlon pneumonla wlLh aLelecLasls around 2 years of deaLh from resplraLory fallure
LffecLlve Lherapy ls noL avallable
AdulL forms muscle weakness occurs laLer
SomeLlmes does noL shorLen llfe expecLancy sedenLary occupaLlon allows
CLhers dle around 30 and 40 year
ls less cardlomegaly normal LCC arrhyLhmla ofLen
ulagnosls blopsy of Lhe skln under an elecLron mlcroscope cerLlflcaLe abnormal lysosomes

G|ycogen storage d|sease type III
Cor| dlsease lorbes dlsease
A8 lmpalred glycogen branchlng enzyme ellmlnaLlng Lhe
8are a slmllar plcLure of a CSu l mllder

G|ycogen storage d|sease type IV
Andersen dlsease
A rare A8 has reporLed abouL 10 cases branchlng enzyme dlsorder
Clycogen ln hepaLocyLes ls a long chaln wlLhouL branchlng (amylopecLln)

Inborn errors of metabo||sm Mucopo|ysacchar|de
1hese dlsorders can be classlfled lnLo groups of lysosomal dlsorders
lay an especlally lmporLanL role Lhese mucopolysaccharldes heparansulfL and keraLansulfL dermaLansulfL
8ecause Lhey are a parL of mucopolysaccharldes blnders are characLerlzed by bone changes (dysosLosls mulLlplex) ls affecLed CnS (menLal
reLardaLlon) as well as kvS llver spleen skln [olnLs and Lendons
Are A8 (wlLh PunLer syndrome (MS ll) ls Lhe x8
ulagnosls of MS ls based on Lhe phenoLype of Lhe chlld ldenLlLy CAC excreLlon ln Lhe urlne xray flndlng dysosLosls enzymaLlc
rognosls ls generally favorable many dylng ln preschool or school age
aLlenLs wlLh mllder forms may llve Lo adulLhood
1herapy excepL for MS l ls a sympLomaLlc

nur|er syndrome (MS I)
AccumulaLlon of dermaLan sulfaLe and keraLan sulfaLe ln Llssues and excreLlon ln Lhe urlne
lL ls Lhe mosL severe MS
uurlng Lhe flrsL year usually flnd only delayed psychomoLor developmenL we can reveal hepaLosplenomegaly kyphosls accenL raLLllng
AfLer 1 ln developlng Lhe sympLoms Lhere ls a Lyplcal face gargololdnl (remlnds gargoyles) macrocephaly promlnenL forehead wlLh
dollchocefalle Lhe nose ls broad and flaL wlLh a deep rooL macroglossla
1here are corneal opaclLles psychomoLor speeds up Lo second year Lhe paLlenL ceases Lo be moblle
ulsablllLy valves kM lnsuff
ueaLh usually ln adolescence
1herapy can be LreaLed by bone marrow LransplanLaLlon

Congen|ta| d|sorders of ||p|d metabo||sm

D|sorders of ox|dat|on of fatty ac|ds
8eLaoxldaLlon plays an lmporLanL role ln ensurlng Lhe energy needs ln perlods of fasLlng
lL ls Lhe dlrecL source of energy for hearL and muscle Llssue and Lhe source of keLone bodles for CnS
ls abouL 20 known dlsorders are A8 Lhe mosL common one MCAu (Medlumchaln acylCoA dehydrogenase) and LCPAu (Longchaln 3
CPacylCoA dehydrogenase)
Cllnlcal plcLure an early chlldhood manlfesL aLLacks of 8eyellke syndrome an acuLe dlsLurbance of consclousness selzures
hepaLomegaly or SluS
8uL may begln laLer ln adulLhood chronlc muscle weakness or kM
LaboraLory LesLs ln Lhe acuLe condlLlon ls ofLen hypokeLoacldoLlck hypoglycemla mlld hypoamonnemle lncreased amlnoLransferase
ln Lhe blood are decreased levels of free and LoLal carnlLlne
lor Lhe MCAu dlcarboxyllc acldurla
lor LCPAu ls a 3CPdlcarboxyllc acldurla
lncreased echogenlclLy of llver sLeaLosls
lor LCPAu ls a load and fever ln Ck and urlne myoglobln
ulagnosls based on an examlnaLlon of Lhe parameLers of beLaoxldaLlon ln lsolaLed lymphocyLes ln comblnaLlon wlLh enzymaLlc and
molecular meLhods
1herapy ls dlfferenL from fallure Lo prevenL sLarvaLlon ln a chlld
lrequenL dleL wlLh resLrlcLlon of faL and one or Lwo porLlons of food aL nlghL
lor MCAu enrlch Lhe malLodexLrlns and sLarches
lor LCPAu nuLrlLlon wlLh faL resLrlcLlon enrlch M1C oll (whlch ls noL buL glve Lhe MCAu)
WlLh fever a hlgher lnLake of sweeLened beverages and Llmely admlnlsLraLlon of CLC
1he lmporLance of carnlLlne ls dlspuLed
rognosls chlldren wlLh unrecognlzed syndrome ofLen dle ln lnfancy under Lhe plcLure of SluS or 8eyellke syndrome
LCPAu may laLer compllcaLe Lhe emergence of reLlnlLls plgmenLosa and kM
aLlenLs ldenLlfled by early dlagnosls and dleLary LreaLmenL have longLerm cllnlcal problems buL Lhe quesLlon of longLerm survlval sLlll
remalns open

D|sorders of p|asma ||poprote|ns
Cne of Lhe mosL common meLabollc dlsorders
SlgnlflcanLly lncrease Lhe rlsk of developlng Cv dlsease wlLh premaLure occurrence of A1 and lM
Culdance for consulLaLlon we wlll deLermlne Chol and 1AC
lor more accuraLe dlagnosls ls necessary Lo collaboraLe wlLh speclallzed deparLmenLs

8are A8 compleLely lacklng llpoproLeln parLlcles conLalnlng Apo8 (chylomlkra vLuL)
1oLal Chol and 1AC levels are low
PeLerozygoLes are easlly
PomozygoLes ln lnfancy faL malabsorpLlon sLeaLorrhea reLarded growLh
LaLer Lhere ls reLlnlLls plgmenLosa and cerebellar aLaxla
ls Lyplcal akanLocyLza (a sLrange hornllke era)
ueflclency of faLsoluble vlLamlns lmpalred corLlsol
Llplds accumulaLe ln Lhe lnLesLlnal eplLhellum vakuoallzace
8ody lacklng essenLlal Mk (llnolelc)
1herapy admlnlsLraLlon of 1AC wlLh medlumchaln (MC1) whlch are absorbed from Lhe lnLesLlne dlrecLly lnLo Lhe porLal clrculaLlon and
vlL ln faLs

Ana|fa||poprote|nm|e (1ang|ersk d|sease)
8educed levels of PuL and ApoAl and lower LuL and LoLal Chol PuL noL only are ApoCll vLuL
Cllnlcal plcLure lL occurs ln lnfancy condlLlonal on Chol esLer accumulaLlon ln Llssues
Lnlarged yellowlsh Lonslls hepaLosplenomegaly and lnfllLraLlon of Lhe cornea
Plgher lncldence of A1

lamlllal comblned hyperllpoproLelnemla
lrequenLly 1200
ApproxlmaLely 1 / 3 of Lhe affecLed famlly members reporLed hlgher Chol 1 / 3 of 1AC and 1 / 3 boLh
LLlopaLhogenesls plays a role ln lncreased formaLlon of vLuL
1herapy sLrlcL dleL focuslng malnly on Lhe measuremenL of cholesLerol
lor chlldren wlLh hyper1AC we musL reduce lnLake of sweeLs

lncrease ln Apo8 componenLs LuL
Levels of LoLal Chol and 1AC are normal

Iam|||a| hypercho|estero|em|a
lallure of Lhe sLrucLure or fce LuL recepLor
Au prevalence ls 1300
Plgher lncldence for Arabs and !ews were lower ln blacks
1ypes of dlsorders LuL8 mosLly mlsslng or ls slowly LransporLed from LC Lo CA or recepLors ls enough buL do noL make LuL or blnd buL
can noL be zanoilL and also glven Apo83300
LuL ls noL absorbed accumulaLes ln Lhe body
1he maln resulL early developmenL of coronary arLery A1
1he flrsL aLLack follows Lhe dlsabled men ls around 40 year Lo Lhe 60Lh ls affecLed by 83 (women abouL 10 more)
1endon xanLhomas (nodular enlargemenL of Lendons) can occur as early as puberLy
ueposlLs ln sofL Llssues (xanLhelesmaLa) such as Lhe eyellds or cornea (arcus corneae) ln adulLhood
1oLal Chol ls above 63 mmol / l
A sLrlcL dleL wlll reduce Chol buL usually normallze
lor chlldren over 6 years served cholecysLamln (resln) dose noL depend on age buL on Lhe degree of cholesLerolemla ls well LoleraLed
even aL hlgh doses
Can cause consLlpaLlon someLlmes vlLamln deflclencles soluble ln faLs
CLher llpld lowerlng ls only sulLable for Lhe LreaLmenL of adulLs
ln homozygous form Lhe prognosls ls poor lM a few years of llfe
Iam|||a| hypera|fa||poprote|nm|e
Plgh PuL syndrome assoclaLed wlLh longevlLy

Inborn errors of metabo||sm of t|ssue ||p|ds ||p|dos|s
1he resulL of lncompleLe enzymaLlc equlpmenL lysosomes
usually accumulaLe glycosphlngollplds
lf Lhey accumulaLe ouLslde Lhe CnS occurs malnly hepaLosplenomegaly (Caucher)
8uL lf Lhey accumulaLe only ln Lhe CnS no hepaLosplenomegaly and Lhe lmage remlnds degeneraLlve braln dlseases (1aySachs)
When Lhey accumulaLe ln Lhe CnS and perlphery boLh (nelmannlck)
1reaLmenL of Lhese dlseases ls unsuccessful poor prognosls

Gaucher d|sease
8educed acLlvlLy of glucocerebrosldase Lhere ls a charglng lysosomal glucosylceramlde ln cells of orlgln makrofgoveho
Cllnlcal plcLure accordlng Lo Lhe course ls dlvlded lnLo Lhree Lypes
nonneuronopaLhlc Lype l Lhe mosL common progresslve splenomegaly hepaLomegaly moderaLe paln ln Lhe long bones speeches
splenlsmu wlLh anemla leukopenla and LhrombocyLopenla wlLh bleedlng manlfesLaLlons ln Lhe skln and subcuLaneous Llssue
AcuLe neuronopaLhlc Lype ll a speech ln lnfanLs fallure Lo Lhrlve sLrablsmus or nysLagmus progresslve hepaLosplenomegaly CnS
lnvolvemenL wlLh Lhe arresL of psychomoLor developmenL and oplsLhoLonus
SubacuLe neuronopaLhlc Lype lll beglns ln Loddlers and preschool affecLlng Lhe CnS buL ls slower Lhan Lype ll
LaboraLory dlfferenL manlfesLaLlons of pancyLopenla
lncreased acLlvlLy chlLoLrlosodzy acld phosphaLase and amlnoLranferz
ln Lhe bone marrow are Caucher cells
1he skeleLal dlsablllLles paLhologlc fracLures verLebral compresslon expanslon of dlsL ends of Lhe femurs and Llbla
1he presence of osLeonecrosls sclnLl
1herapy LreaLmenL of cholce for Lype l and lll ls prepared recomblnanL enzyme Ceresyme

N|emann|ck d|sease
A heLerogeneous group of dlseases leadlng Lo excesslve charglng lyzosomlnlmu sflngomyellnu A8
Cllnlcal plcLure already ln lnfanLs fallure Lo Lhrlve hepaLosplenomegaly and lymphadenopaLhy ln Lhe flrsL weeks of prolonged [aundlce
gradually progresslve neurodegeneraLlve dlsorders psychomoLor reLardaLlon spasLlc kvadrupareza
ulagnosls charglng sfyngomyellnu hlsLopaLhologlcal flndlngs and oLher llplds ln cells penovlLych ln Lhe marrow (nlemannlck cells)
lrequenL ls Lhe presence of a cherry sLaln Lhe reLlna
1herapy bone marrow LransplanLaLlon (only for Lype 8 vlsceral moderaLe dlfflculLy)

c Loss of appet|te

Causes organ|c and |norgan|c
lnfecLlon nSZ
8raln 1umors
MeLabollc defecLs (aclds fall lnLo cenLers for vomlLlng whlch ls ouLslde Lhe PL8)
Anorexla nervosa bullmla

Nonorgan|c |oss of appet|te
1hlnk of Lhe psychologlcal orlgln Lo Lhe excluslon of organlc dlsorders
MosL common ln Loddlers and preschool age
SCS vlllages and orphanages only very rarely lLs a quesLlon of Lhe relaLlonshlp of parenLs Lo Lhe chlld
?ou need Lo make parenLs undersLand Lhelr own aLLlLudes
1he amounL of food Lhe chlld has recelved a greaL psychologlcal lmporLance for parenLs
lL ls proof of lLs vlLallLy healLh
lL ls conflrmaLlon of Lhe success of parenLs as educaLors
lL ls for Lhem a source of deep saLlsfacLlon
Cn Lhe conLrary lf a chlld refuses food
leellngs of frusLraLlon lnsecurlLy anxleLy frusLraLlon wlLh parenLs parenLs Lhen Lend Lo use vlolence agalnsL Lhe chlld requlre
medlcal lnLervenLlon
Such behavlor leads Lo a chlld even sLronger flxaLlon re[ecLlng aLLlLudes
1he chlld LhaL Lhelr behavlor ln facL domlnaLes Lhe whole famlly ls aL Lhe cenLer of aLLenLlon
lf Lhe parenLs accepL Lhls lnLerpreLaLlon and Lake furLher advlce and can be furLher addressed
noL all of lL can have dlfferenL subconsclous defense mechanlsms
We lead Lhe parenLs Lo domlnaLe Lhelr efforLs Lo nurLure a chlld accordlng Lo Lhelr wlshes
1herapy food should be LasLy [ulcy welldecoraLed
We do noL compleLely conform Lo Lhe LasLes of Lhe chlld buL noL Lo worry hlm very much Lo meeL
Cn a plaLe of food Lo be so much a chlld can really eaL
8efore Lhe chlld can sLlll remove a small porLlon of food
LaLlng dlsorders anorexla anorexla blnge eaLlng vomlLlng mornlng