[Met/UCD/Basic]
Five catalytic enzymes in Urea cycle?
- Carbamoylphosphate synthetase I (CPS1)
- Ornithine transcarbamylase (OTC)
- Argininosuccinic acid synthetase (ASS1)
- Argininosuccinic acid lyase (ASL)
- Arginase (ARG1)
[Met/UCD/Basic]
One cofactor-producing enzyme in Urea Cycle?
N-acetyl glutamate synthetase (NAGS)
[Met/UCD/Basic]
Two amino acid transporters in Urea Cycle?
- Ornithine translocase (ORNT1; ornithine/citrulline carrier)
-> Hyperammonemia, hyperornithinemia, homocitrullinuria - Citrin (aspartate/glutamate carrier)
-> Citrullinemia type II
[Met/UCD/Basic]
Urea cycle disorder in order of prevalence in USA? (5)
Ornithine transcarbamylase (OTC) deficiency
Citrullinemia type I (ASS1 deficiency)
Argininosuccinic aciduria (ASL deficiency)
Carbamoyl phosphate synthetase 1 (CPS1) deficiency
Arginase deficiency
[Met/UCD/Basic]
Classic presentation of hyperammonemia in urea cycle disorder? (3)
- Birth history
- Age
- Presentation
Normal term newborn
By 5 days of age
Hypotonia, vomiting, lethargy, coma
[Met/UCD/Basic]
Secondary hyperammonemia in IEMs (5)
- Organic acidemias
- Fatty acid β-oxidation defects
- Mitochondrial respiratory chain defects
- Primary lactic acidosis (pyruvate carboxylase deficiency, pyruvate dehydrogenase deficiency)
- Carbonic anhydrase VA (CAVA) (bicarbonate donor to CPS1 and to mitochondrial carboxylases)
[Met/UCD/Basic]
Non-IEM causes of hyperammonemia (5)
- Transient hyperammonemia in the newborn
- Liver failure
- Portocaval shunts
- Urease-producing bacteria (UTI, overgrowth of bowel flora)
- Drug-related (valproate, PEG-asparaginase)
- Massive tissue necrosis (e.g., leukemia treatment, post-transplant)
[Met/UCD/Basic]
Typical ammonia level in classic urea cycle disorder?
> 1,000 mmol/L
[Met/UCD/Basic]
Hemodialysis indication ammonia level in urea cycle disorder
Hemodialysis if ammonia > 200 mmol/L
[Met/UCD/Basic]
Typical blood gas finding in classic urea cycle disorder?
Respiratory alkalosis
(Hyperventilation secondary to the effect of hyperammonemia on the brain stem)
[Met/UCD/Basic]
Other initial lab findings in classic urea cycle disorder (4)?
- Respiratory alkalosis
- Low BUN (low blood urea)
- Mildly elevated liver enzymes
- +/- coagulopathy
[Met/UCD/Basic]
Commonly elevated amino acids in all urea cycle disorder? (3)
Alanine
Asparagine
Glutamine
[Met/UCD/Basic]
Biochemical testing for urea cycle disorder? (3)
Plasma amino acid analysis
Urine amino acid analysis
Urinary orotic acid
[Met/UCD]
Which urea cycle defect?
Citrulline: Absent or low
Orotic acid: Very high
Ammonia: Very high
Arginine: Low
Ornithine transcarbamylase (OTC) deficiency
[Met/UCD]
Distinguishing metabolite between Ornithine transcarbamylase (OTC) deficiency and Carbamoyl phosphate synthetase 1 (CPS1) deficiency?
Ornithine transcarbamylase (OTC) deficiency: High orotic acid
Carbamoyl phosphate synthetase 1 (CPS1) deficiency: Low orotic acid
(Carbamoyl phosphate -> orotic acid)
[Met/UCD]
Which urea cycle defect?
Citrulline: Absent or low
Orotic acid: Low
Ammonia: Very high
Arginine: Low
Carbamoyl phosphate synthetase 1 (CPS1) deficiency
N-acetyl glutamate synthetase (NAGS) deficiency
Carbonic anhydrase VA (CA-VA) deficiency (high lactate)
[Met/UCD]
Which urea cycle defect?
Citrulline: High
Orotic acid: High
Ammonia: High
Arginine: Low
Argininosuccinic acid: present
Argininosuccinic aciduria (ASL deficiency)
[Met/UCD]
Which urea cycle defect?
Citrulline: Very high
Orotic acid: High
Ammonia: High
Arginine: Low
Argininosuccinic acid absent
Citrullinemia type I (ASS1 deficiency)
[Met/UCD]
Which urea cycle defect?
Citrulline: Normal
Orotic acid: Normal
Ammonia: Normal
Arginine: Very high
Arginase deficiency
[Met/UCD]
Which condition has Fragile hair (trichorrhexis nodosa)?
Argininosuccinic aciduria (ASL deficiency)
[Met/UCD]
Typical symptoms of arginase deficiency (3)
- Progressive neurocognitive course
- Spastic diplegia
- Failure to thrive
[Met/UCD/HHH]
Typical symptoms of Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome (ORNT1 Deficiency) (4)?
- Acute encephalopathy secondary to hyperammonemic crisis
- Chronic neurocognitive deficits, Spasticity, Ataxia
- Chronic liver dysfunction
- Hyperornithinemia with gyrate atrophy of the choroid and retina
[Met/UCD/Citrin]
Three types of Citrin deficiency (Citrullinemia type II)? (3)
- Neonates
- Children
- Adolescence
- NICCD: Neonatal intrahepatic cholestasis
- FTTDCD: childhood, failure to thrive and dyslipidemia
- CTLN2: adolescent, adulthood, recurrent hyperammonemia with neuropsychiatric symptoms
[Met/UCD/Citrin]
Typical food aversion in citrin deficiency (Citrullinemia type II)?
Sugar aversion
+/- alcohol
(malate-aspartate shuttle, preventing proper liver energy production from carbohydrates)
