Question 9.1

A 51 -year-old female presents with a decreased conscious state, Glasgow Coma Scale (GCS) 12, confusion and myoclonus. She is on treatment for a seizure disorder. Her CT brain scan shows no acute intracranial abnormality.

Her investigations are as follows:


Patient Value

Adult Normal Range


1 38 mmol/L



4.1 mmollL

3.5 - 5.2


18 mmol/l_•

22 - 32


14.2 mmoVL•

3.0 - 8.0


210 mol/l_•

45 - 90


54 mol/L*

< 20

Alanine transferase


< 35

Aspartate transferase


< 35

Alkaline phosphatase

103 Ull-

30- 110

Glutam transferase

67 U/L*

< 40





61 IL

60 - 80



< 50


List  possible causes of the hyper-ammonaemia in this patient.  (40% marks)

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College answer

  • Liver failure
  • Anti-epileptic drugs – Sodium valproate and Carbamazepine
  • Other drugs / toxins eg paracetamol, salicylates, mushrooms
  • Urosepsis with urea-splitting organisms e.g. Klebsiella, Proteus
  • Urea-cycle disorders (Patients with high ammonia from drugs or urosepsis usually have undiagnosed mild disorders of urea-cycle metabolism)


The patient; she is probably on valproate for her seizure disorder. Valproate overdose is a logical explanation for a decreased level of consciousness, myoclonus and high ammonia.

Causes of hyperammonaemia more broadly could be any of the following:

Pre-analytical error

  • Prolonged pre-transport time
  • Room temperature storage of sample

Increased substrate for ammoniagenesis

  • Excess protein catabolism:
    • Essential amino acid deficiency
    • Primary dietary carnitine deficiency
    • Steroids
    • Immobility
    • Severe exercise
    • Increased tissue turnover, eg haematological malignancy
  • Excess protein intake:
    • Weird diet
    • Parenteral nutrition

Bypass of normal metabolism

  • TIPS procedure
  • Portosystemic shunts

Acquired urea cycle defects

  • Fulminant hepatitis of any cause
  • Reye's syndrome
  • Drugs, eg. glycine or valproate

Congenital urea cycle defects

  • Inherited urea cycle defects
  • Organic aciduria
  • Fatty acid oxidation defects

Excess of exogenous ammonia

  • Ammonium chloride therapy
  • Excess generation of ammonia:
    • Gastric bypass
    • Urease-producing organisms
    • UTI

Reabsorption of excreted ammonia

  • Distal renal tubular acidosis
  • Ureteric diversion
  • Urinary tract infections
  • Vesicoureteric reflux
  • Bladder perforation


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