Genetic defect have been described in all enzymes of urea cycle – results in ammonia intoxication.

These are extremely rare : 1 in 30,000 live births.

Key Points of Urea Cycle Disorders is Characterized by:

• Hyperammon
• Hyperammonemia
• Encephalopathy
• Respiratory alkalosis.

Clinical  Symptoms:

1. Neonatal  period: Feeding difficulties, Lethargy, irritability, protein induced vomiting and poor intellectual development ,cerebral edema, seizures leads to COMA and death.
2. Infants and older children:  Vomiting,Neurologic abnormalities (ataxia, mental confusion,agitatiory irritability, and combativeness).

BIOCHEMICAL DEFECT IN UREA CYCLE DISORDERS

• Ammonia intoxication is most severe in the deficiency of first two enzymes. Because once citrulline synthesized some ammonia is already been covalently linked to an organic metabolite.
• Deficiency  of any  of the  urea  cycle  enzyme would  result  in  hyperammonemia.
• All of the  disorders are  inherited  as  autosomal  recessive  pattern,  except  hyperammonemia  type  II  (ornithine transcarbamoylase  deficiency) which  is  an X-linked disorder.

Hyperammonemia  may be due to:

• Excessive  amount  of α-ketoglutarate from  citric  acid  cycle  is  used  to  form  glutamate.
• This results  in decreased  α-ketoglutarate available  for  TCA cycle.
• leading  to  inhibitionof  TCA cycle  and ATP  production.
• Increased  formation  of GABA (gamma-Aminobutyric acid) from  glutamate  leads  to  impaired  neural  transmission process.
• Increased  glutamine  produces  osmotic effect  that leads  directly  to  swelling  of  the  brain.

Treatment:

• Benzoic  acid was used in  treatment  of hyperammonemia.
• Benzoic  acid  combines  with  glycine  to  form  Hippuric acid(C9H9NO3)  which can  remove  nitrogen in  urine.
• This provides  an  alternative  route  for  nitrogen excretion.

Don’t Forget to Solve all the previous Year Question asked on Disorders of urea cycle