Urea Cycle Defects

Question 1

Clinical Presentation of neonatal onset urea cycle defects

Answer 1

Age of onset: >24 hrs of age
Lethargy
Poor feeding
Vomiting
Seizures
Bleeding
Hyperventilation
Coma
Death

Question 2

Differential diagnosis of lethargic newborn

Answer 2

Sepsis
Congenital defect (heart, brain)
Inborn error of metabolism

Question 3

Urea Cycle Defects: treatment

Answer 3

RESTRICT SUBSTRATE
- essential amino acid formulas
PROVIDE PRODUCT
- arginine or citrulline
REPLACE ENZYME:
- liver transplant
PROVIDE ALT ROUTES OF ELIMINATION:
- ammonia scavengers
   - i.e. benzoate, phenylacetate
TREAT SECONDARY EFFECTS
- increased intracranial Pressure, DIC, etc

Question 4

Hyperammonemic encephalopathy

Answer 4

damage to brain as result of hyperammonemia
usually recur despite therapy
Triggers include:
- intercurrent infection
- fasting
- protein loads
- surgery

Question 5

Compare the following:

• OTC deficiency
• Arginosuccinate lyase deficiency
• Argininemia

Answer 5

OTC deficiency:
- X-linked; more mild in females

Arginosuccinate Lyase:
- typical coarse hair, cirrhotic changes

Argininemia:
- most develop severe lower limb spasticity

Question 6

Later-onset urea cycle defects

Answer 6

usually caused by less severe mutations and better residual enzyme activity

Signs and symptoms:

• mental retardation
• recurrent vomiting
• failure to thrive
• Recurrent coma
• History of protein aversion