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

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

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