HYPERAMMONEMIA

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Presentation by,
Nishanthi
20368038
M.Sc., I year
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Hyperammonemia
• Hyperammonemia is a metabolic condition
characterized by the raised levels of ammonia, a
nitrogen- containing compound.
• Hyperammonemia is a biochemical sign of failure of
the liver and defects in urea cycle enzymes.
• Hyperammonemia may be acquired or congenital.
• Brain is very sensitive to ammonia. Brain tries to fix
ammonia as glutamine.
• Glutamine synthetase is energy consuming and TCA
cycle intermediate alpha-ketoglutarate is also
depleted.
• Persistent hyperammonemia will leads to irreversible
neuronal damage, neuronal swelling and coma.
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Hyperammonemia Type I
• Carbamoyl phosphatase synthetase 1 deficiency (CPS1
deficiency) .
• It is the most severe of the urea cycle disorders.
• Enzyme deficit- CPS1
• Features- Very high ammonia levels in blood; autosomal
recessive. Mental retardation. Incidence is 1 in 100,000.
Hyperammonemia Type II
• Ornithine transcarbamylase deficiency (OTC).
• The only recessive x- linked encoded enzyme.
• Enzyme deficit- OTC
• Features- High level of ammonia in blood, Increased glutamine in
blood, CSF and urine. Orotic aciduria due to channeling of
carbamoyl phosphate into pyrimidine synthesis. .
Hyperammonemia Type III
• N- acetyl glutamate synthase deficiency.
• It is inherited as an autosomal recessive trait which
results in a reduced acitivity of carbamoyl
phosphate synthetase I.
• Features- Subsequent accumulations of neurotoxic
ammonia; elevated level of glutamine and alanine
in blood plasma.
Acquired Hyperammonemia (Hepatic Coma)
• Hyperammonemia is the characteristic feature of
liver failure. The condition is also known as portal
systemic encephalopathy.
• The signs and symptoms are mainly pertaining to
CNS dysfunction (altered sensorium, convulsions) or
manifestations of failure of liver function (ascites,
jaundice, hepatomegaly, edema, hemorrhage, spider
naevi).
• The management of the condition is difficult. .
Symptoms
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Management of Hyperammonemia
• Restrict protein intake and supplement with alpha keto acids which can be
transaminated.
• Lactulose will reduce ammonia production from gut in hepatic
encephalopathy.
• Administration of phenylacetate has been found to ne useful since it can
conjugate with glutamine and glycine, forming phenylacetylglutamine and
hippurate. This will excrete more ammonia nitrogen in a nontoxic form.
This is only an adjunct to therapy.
• Gene therapy to correct the urea cycle disorder is still under trial.

Normal level of ammonia in blood is very low, <50 µg/dl or 10-40 µmol/L.
Total soluble ammonia is only 150 µg/5L of blood volume. Even a mild
elevation in ammonia level should not be ignored.
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Questions
1. Transamination of Glutamic acid produces what? Alpha-.
ketoglutaric acid.
2. Which amino acid is oxidatively deaminated in liver?
Glutamic acid.
3. Ammonia is trapped in brain by what? Glutamine
synthetase.
4. What are the two- carbamoyl phosphate synthetases? CPS
I is involved in urea synthesis and seen in mitochondria;
CPS II is required for pyrimidine synthesis and present in
cytosol. .
References .
• Textbook of Biochemistry - DM Vasudevan.
• Textbook of Biochemistry – Satyanarayana
• Ali R, Nagalli S, 2020,Hyperammonemia
• Ari Auron, Patrick D Brophy, 2011, Hyperammonemia in
review: pathophysiology, diagnosis and treatment, Pediatr
Nephrol, EDUCATIONAL REVIEW, DOI 10.1007/s00467-011-
1838-5.

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