Urea Cycle Disorders

Question 1

N-Acetylglutamate Synthase deficiency (NAGS)

Answer 1

• Autosomal recessive
• Lethargy, persistent vomiting, poor feeding, hyperventilation, enlarged liver, seizures
• Total deficiency - symptoms appear immediately following birth
• Partial deficiency - may occur later in life following a stressful event such as infection
• Low cirtulline levels, normal orotic acid levels

Question 2

Carbamyl phosphate synthetase deficiency (CPS)

Answer 2

• Autosomal recessive
• Lethargy, coma, seizures, vomiting, poor feeding, hyperventilation, heptaomegaly
• Total deficiency - symptoms appear immediately following birth
• Partial deficiency - symptoms appear in childhood
• Low citrulline levels, normal orotic acid levels

Question 3

Ornithine transcarbamylase deficiency (OTC)

Answer 3

• X-linked
• Most common
• Lethargy, coma, seizures, vomiting, poor feeding, hyperventilation, hepatomegaly
• Hemizygote males - onset immediately after birth
• Hemizygote females - 10% are symptomatic
• Low citrulline levels, high orotic acid levels

Question 4

Argininosuccinic acid synthetase deficiency (ASS) :)

Answer 4

• Autosomal recessive
• Lethargy, coma, seizures, vomiting, hyperventilation, poor feeding, hepatomegaly
• Total deficiency - symptoms appear immediately following birth
• Partial deficiency - symptoms appear in childhood
• High citrulline levels, high orotic acid levels

Question 5

Argininiosuccinic acid lyase deficiency (ASL)

Answer 5

• Autosomal recessive
• Lethargy, coma, seizures, vomiting, hyperventilation, poor feeding, hepatomegaly
• Total deficiency - symptoms appear immediately following birth
• Partial deficiency - symptoms appear in childhood
• High citrulline levels, high orotic acid levels

Question 6

Arginase Deficiency (ARG)

Answer 6

• Autosomal recessive
• Delayed development, protein intolerance, spasticity, seizures, irritability, vomiting, poor appetite
• Slower onset, often present with symptoms of muscle weakness, hyperammonemia is rare
• High citrulline levels, high orotic acid levels

Question 7

Treatment of Urea Cycle Defects

Answer 7

• Goal is to maintain plasma glutamine levels at or near normal (Glutamine represents a storage form of nitrogen that can buffer ammonium)
• Measure of plasma glutamine levels may be single best guide to therapy (levels can predict hyperammonemia)
• Restricted intake of dietary protein
• Activation of other waste nitrogen pathways - CPS, OT, ASS - sodium phenylbutyrate activates phenylacetylglutamine - new vehicle for removal of waste nitrogen
• Arginine supplementation in ASS and ASL
• Ammonul medication
• Liver transplant in severe phenotypes