5 urea cycle defects 1

CPS Deficiency

Autosomal recessive disorder of amino acid metabolism

Enzyme Defect: Carbamoyl phosphate synthetase (CPS I)

Clinical Presentation: sleepiness, poorly regulated breathing rate or body temperature,

unwillingness to feed, vomiting after feeding, unusual body movements, seizures, or coma

Severe: Onset within first few days after birth

Mild: Onset later in life

Lab Findings: ↑Ammonia, ↑CSF Glutamine, Respiratory alkalosis, Low BUN, ↑Glutamine, alanine, asparagine, ↓Citrulline ↓Arginine, ↓Urine orotic acid

Diagnostic Test

Ammonia

Plasma and urinary organic acids

Treatment: Protein restricted diet

Acute: If infant in a coma & plasma ammonia > 500 mM/L, hemodialysis is the only way to clear ammonia

Chronic: High calorie, protein restricted diet with or without additional amino acids

Infantile onset has increasing patients undergoing liver transplants with improved outcomes

Long term Prognosis: Survival beyond newborn period: recurrence of elevated ammonia. Delayed development and intellectual disability

Ornithine Transcarbomylase (OTC) Deficiency

X-linked disorder of nitrogen waste removal - 1:70,000 (most common UCD)

Enzyme Defect: Ornithine Transcarbamylase (chromosome Xp11.4)

Clinical Presentation: Lethargy, hypotonia, vomiting and poor feeding. Death if undiagnosed

Lab Findings: ↑Ammonia (> 700 mM/L), ↑CSF Glutamine, Respiratory alkalosis, Low BUN, ↑Glutamine, Alanine, Asparagine, ↓Citrulline, ↓Argninine, ↑Urine orotic acid (diagnostic)

Diagnostic Test

Ammonia

Quantitative plasma and urinary organic acids

Treatment:

Acute: If infant in a coma & plasma ammonia > 200 mM/L, hemodialysis is the only way to clear ammonia

Chronic: High calorie, protein restricted diet with or without additional amino acids

Infantile onset has increasing patients undergoing liver transplants with improved outcomes