Urea Cycle Defects

Question 1

When should you suspect an IEM?

Answer 1

• Abnormal newborn screening result
• Difficulty feeding, FTT
• Developmental delay, regression
• FHx: SIDS, early and/or sudden death, consanguinity
• Multiple organ systems involved: seizures, hyper/hypotonia,
  recurrent URI, valvular disease

Question 2

What are acute symptoms of urea cycle disorders?

Answer 2

Seizures, Coma, Brain Edema, Death

Question 3

What are long term symptoms of urea cycle disorders?

Answer 3

Cognitive Impairment/Intellectual Disability, Spastic Quadriplegia, Ataxia

Question 4

What is the treatment during a urea cycle defect crisis?

Answer 4

• No protein
• Dextrose Containing IVF + IL
• Ammonul + IV Arginine
• Dialysis

Question 5

What is the long term treatment for urea cycle defects?

Answer 5

• Protein Restricted Diet
• Ammonia Scavengers
• Liver Transplant
• Gene Therapy?

Question 6

What are signs and symptoms of hyperammonemia?

Answer 6

• Headache
• Personality and Behavioral changes
• Sleep disorders
• Anorexia
• Vomiting
• Confusion
• Psychomotor agitation
• Delusions
• Hallucinations
• Slurred speech

Question 7

What are the Urea Cycle Enzyme disorders?

Answer 7

• N-Acetylglutamate Synthetase Deficiency
• Carbamyl Phosphate Synthetase I Def.
• Ornithine Transcarbamylase Deficiency
• Argininosuccinate Synthetase Deficiency
• Argininosuccinate Lyase Deficiency
• Arginase Deficiency

Question 8

N-acetylglutamate Synthase Deficiency (NAGS)

Answer 8

Gene: NAGS on chromosome 17q21
Frequency: Unknown
Inheritance: Autosomal Recessive

Question 9

Carbamyl Phosphate Synthetase I Deficiency (CPS1)

Answer 9

Gene: CPS1 on chromosome 2q34
Frequency: 1/62,000
Inheritance: Autosomal Recessive

Question 10

Ornithine Transcarbamylase Deficiency (OTC)

Answer 10

Gene: OTC on chromosome Xp21.1
Frequency: 1/14,000
Inheritance: X-linked

Question 11

Argininosuccinate Synthetase Deficiency (Citrullinemia)

Answer 11

Gene: ASS1 on chromosome 9q34.11
Frequency: 1/57,000
Inheritance: Autosomal recessive (AR)

Question 12

Argininosuccinate Lyase Deficiency (ASL)

Answer 12

Gene: ASL on chromosome 7q11.21
Frequency: 1/70,000
Inheritance: Autosomal recessive (AR)

Question 13

Arginase Deficiency (Argininemia)

Answer 13

Gene: ARG1 on chromosome 6q23.2
Frequency: 1/350,000
Inheritance: Autosomal recessive (AR)

Question 14

What biochemical testing do you do when you suspect a urea cycle disorder?

Answer 14

Plasma amino acids
Ammonia levels
Orotic acid

Question 15

What elevation on biochemical testing would we expect to see in OTC that we wouldn’t see in other urea cycle disorders?

Answer 15

Orotic acid

Question 16

What urea cycle disorder is X-Linked?

Answer 16

OTC

Question 17

What urea cycle disorder is NOT on NBS?

Answer 17

OTC