Download - Inborn Errors of Urea Cycle Trans
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8/3/2019 Inborn Errors of Urea Cycle Trans
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Creators: D2.Grp 1 Alejado, Ruby Joy; Ramos, Voltaire; Sagle, Maria Josefina; Soriano, Ellison; Tandayu, Nicolle Ann 2012
Inborn Errors of Urea Cycle Trans
I. The Urea Cycle
Step Enzyme Location Substrate Product Deficiency
1 Carbamoyl phosphatesynthetase I
Mitochondria NH3 + CO2 + 2ATP
Carbamoylphosphate
Hyperammonemiatype I
2 Ornithinetranscarbamoylase
Mitochondria Carbamoylphosphate +Ornithine
Citrulline Hyperammonemiatype II
3 Arginosuccinate synthetase Cytosol Citrulline +aspartate + Mg-
ATP
Arginosuccinate+ AMP + Mg-PPi
Citrullinemia
4 Arginosuccinase Cytosol Arginosuccinate L-arginine +fumarate
Arginosuccinuria
5 Arginase Cytosol L-arginine + H2O L-ornithine +urea
Arginemia
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Creators: D2.Grp 1 Alejado, Ruby Joy; Ramos, Voltaire; Sagle, Maria Josefina; Soriano, Ellison; Tandayu, Nicolle Ann 2012
II. Inborn Errors of Urea Cycle
> deficiencies of the enzymes involved in urea cycle
> common symptoms are due to hyperammonemia and ammonia intoxication is characterized by:
a. tremors c. blurring of vision e. irritability g. death
b. slurring of speech d. vomiting f. hepatic coma
Enzyme
Deficient
Deficiency Unique S/S Transmission Dx Tx
CPS I Hyperammonemiatype I
- clinicalmanifestationindistinguishablewith OTCdeficiency- severe: onset canbe seen in neonatalperiod
Autosomalrecessive
-geneanalysis forpre-nataldiagnosis
- nutritional restriction of protein- administration of
ARGININE/CITRULLINE andSODIUM BENZOATE/SODIUMPHENYLACETATE
OTC Hyperammonemiatype II
- Male patientsusually showclinically severesymptoms atyounger ages thanfemale patients- most severe:increase of NH3 1-
3 days after birth- frequent elevationof NH3 blood level= occasionallyelevate to life-threatening level
X-linked - amino acidanalysis- High levels:> NH3> GLN/GLU>ORNITHINE(not
essential)- LOWlevels:> Citrulline> Arginine
Mild > nutritionalrestriction of protein
> oraladministration ofcitrulline andarginine
Severe
> acuteattack inadult> NH3reach life-threatening
> infusion of
effective amino acid(arginine)> drugs to employalternativepathways ofeliminating nitrogen(SODIUMBENZOATE and
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Creators: D2.Grp 1 Alejado, Ruby Joy; Ramos, Voltaire; Sagle, Maria Josefina; Soriano, Ellison; Tandayu, Nicolle Ann 2012
SODIUMPHENYLACETATE)
> liver transplant
Arginosuccinatesyntethase
Citrullinemia - extremely highcitrulline blood level- very low arginineblood level
Autosomalrecessive
- amino acidanalysis
- nutritional restriction ofprotein intake- administration of arginine
Arginosuccinase Arginosuccinuria - increased
arginosuccinate inblood and urine- hepatomegaly- kinky hair
Autosomal
recessive
- amino acid
analysis
- restriction of arginine and
protein is effective
Arginase Arginemia - spastic paraplegia- accumulation ofarginine- intractable mentalretardation
Autosomalrecessive
- amino acidanalysis ofplasma
- protein restriction