Urea Cycle Disorders

Question 1

CPS I deficiency (Hyperammonemia Type I)

Answer 1

• hyperammonemia
• neurological manifestations
• seizures and mental retardation (if untreated)
• lethargy, irrritability, feeding difficulties

sometimes responds to Arginine intervation (formation of NAG- absolute activator of CPS I)

• high levels of NAG might work
• dialysis
• Benzoic acid (cominbes with glycine to form Hippuric acid- excreted in urine)

-Phenylbutyrate (converted to phenylacetate)
converted to phenylacetate
condenses with glutamine 
form phenlacetylglutamine 
excreted in urine 
removes 2 N per molecule 

low protein high carb diet

Question 2

OTC deficiency (Type II Hyperammonemia)

Answer 2

most common (more common and severe in males)

X-linked

-elevated serum ammonia
-elevated serum & urine orotic acid
(orotic acid b/c high carbomyl phosphate)

Question 3

Arginosuccinate synthase deficiency (Classic Citrullinemia)

Answer 3

hyperammonemia
high levels in citrulline in urine and serum

treatment may include arginine (enhances urinary citrulline excretion)

sometimes allow urea cycle to continue (due to high level of substrate)

Question 4

Arginosuccinate lyase deficiency (Arginosuccinic Aciduria)

Answer 4

hyperammonemia
elevated plasma/CSF arginosuccinate
moderatly high levels of citrulline
arginosuccinate in urine

treated with surplus arginine (allows urinary excretion of arginosuccinate)

Question 5

Arginase Deficiency (Hyperargininemia)

Answer 5

hyperammonemia (blood levels of ammonia not as high as other UCD’s)
elevated arginine

diet of essential amino acids (excluding arginine)

adult onset
neurological problems

Question 6

Aquired Hyperammonemia

Answer 6

cirrhosis (no porto-system shunting; portal blood enters systemic circulation)

Ammonia from intestine directly enters circulation

Treatment
-low protein/high carb diet

Lactulose (A disaccharide)

• resistent to digestion in SI
• bacteria in colon digest lactic acid
• acid neturalized by NH4+
• more N excreted in feces

Neomycin

• antibiotic treatment
• reduction in bacterial ureases