Topics in Genetic Counseling - Urea Cycle

Which macromolecular represents the primary source of nitrogen in the cell?

• nucleic acids

• proteins

• carbohydrates

• lipids

Urea cycle disorders in total have a general incidence of 1:35,000. Which of these urea cycle disorders is the most common?

• ASS1 deficiency

• NAGS deficiency

• CPS1 deficiency

• OTC deficiency

• ASL deficiency

Answer explanation

OTC deficiency occurs at 1:56,000

Urea cycle disorders are typically inherited by what pattern with the major exception being OTC deficiency?

• autosomal dominant

• autosomal recessive

• X linked recessive

• mitochondrial

• X linked dominant

When we think of urea cycle disorders, there are proximal and distal types. How can we distinguish these?

• Proximal: mostly on NBS, detected by low citrulline

  Distal: mostly on NBS, detected by high citrulline

• Proximal: mostly on NBS, detected by high citrulline

  Distal: not on NBS, detected by low citrulline

• Proximal: not on NBS, detected by low citrulline

  Distal: mostly on NBS, detected by high citrulline

• Proximal: not on NBS, detected by high citrulline

  Distal: not on NBS, detected by low citrulline

Match the following urea cycle disorders to its respective change in biochemical readings on an NBS.

• high ammonia, low orotic acid

• arginosuccinate lyase deficiency

• normal ammonia

• ornithine transcarbamylase deficiency (OTC)

• high ammonia, high citrulline

• N-acetylglutamate synthatase deficiency

• high ammonia, high orotic acid, low citrulline

• arginase deficiency

Match the following urea cycle disorders to its respective unique and distinguishing feature.

• X-linked; seen in males more frequently

• arginosuccinate lyase deficiency

• trichorrhexis nodosa; breakable hair

• N-acetylglutamate synthatase deficiency

• progressive spasticity; stiffness due to neurological issues

• arginase deficiency

• specific oral medication available; Carbaglu

• ornithine transcarbamylase deficiency (OTC)

A 2 year female is brought into clinic with lethargy/sleepiness, vomiting and seizures. Blood work shows ammonia 222.4 uM (Norm = 9-33 uM) and citrulline 7.7 uM (Norm = 7-35 uM) and orotic acid 0.1 uM (Norm = 1.5-5.5 uM). What genetic testing should you order?

• OTC

• ARG1

• NAGS/CP1

• ASS1

• ASL

Based on the pedigree shown, what testing is most appropriate for the index case given that they have a history of high ammonia and citrulline but low orotic acid.

• NAGS/CPS1

• ASS1

• ARG1

• OTC

• ASL

If the index case parent asked what the risk was to his young daughters for a urea cycle defect, how would you counsel based on the inheritance?

• They have no risk.

• They have a risk of around 45% of showing severe symptoms.

• They have a risk of around 15% with variable severity.

• They have a 75% risk of showing mild symptoms.

• They have a 30% of showing severe symptoms.

Match the following urea cycle defect fact pairs to each other.

• UCD later in life

• Ultimate treatment for UCD's

• nitrogen scavengers

• 
• sick neonate with UCD

• Emergency treatment

• Fruit with high levels of citrulline

• Classic presentation

• liver transplant

• Mild presentation