TYPES OF HYPERAMMONEMIA

N-Acetylglutamate Synthetase Deficiency (NAGS)

N-acetylglutamate synthetase deficiency affects the body’s ability to make n-
acetylglutamate (NAG) which is a required cofactor for the function of carbamyl
phosphate synthetase I. Without NAG, CPSI cannot convert ammonia into carbamyl
phosphate. Along with OTC deficiency and CPSI, deficiency of N-acetylglutamate is
the most severe of the urea cycle disorders. Patients with complete NAGS deficiency
rapidly develophyperammonemia in the newborn period. A new experimental
treatment for this disease is currently under investigation through the Urea Cycle
Disorders Consortium using the compound carbamyl glutamine.
Carbamoylphosphate synthetase I deficiency (CPS-I Deficiency)
Carbamylphosphate synthetase I deficiency affects the livers ability to convert nitrogen
to urea. This enzyme takes ammonia and through the use of bicarbonate and ATP
produces carbamyl phosphate. This enzyme requires the presence of its cofactor n-
acetylglutamate.. Patients with complete CPSI deficiency rapidly
develophyperammonemia in the newborn period.
Ornithine Transcarbamylase (OTC) Deficiency:
OTC deficiency is the most severe of the urea cycle disorders. Patients with complete
OTC deficiency rapidly develop hyperammonemia in the newborn period.
SIGNS :
•Initially healthy appearing neonate with decompensation after several days
•Often seen after institution of protein feedings
•Lethargy
•Poor feeding
•Vomiting
•Hypotonia
•Respiratory distress, tachypnea, apnea
•Irritability
•Seizure activity
•Neurologic deterioration leading to coma
•Death
Long Term Effects of Neonatal Ammonemia :
•Demonstrated correlation between prolonged neonatal hyperammonemic coma and
brain damage with impaired intellectual functioning
•Did not demonstrate correlation between peak ammonia level and level of
intellectual impairment
•The diagnosis of Hyperammonemia involves identifying the cause of the condition.
Medical examination should include:
•Liver function tests
•Coagulation tests
•Measurement of acetaminophen levels
•Viral serologies
•In case of a suspected IEM, patients should undergo medical tests that evaluate the
levels of organic acid, amino acids and orotic acid in the urine. A liver biopsy may be
considered for confirmation of the diagnosis of the disease. Quantitative plasma and
Carnitine evaluation should also be done.
•If an acute liver failure is suspected due to drug usage, the social history should be
considered and a careful medical treatment has to be carried out. Abdominal CT
scanning may help in an accurate diagnosis.
•The differential diagnosis of Hyperammonemia should aim at distinguishing the
condition from other similar disorders, such as
Portal vein thrombosis
Fatty infiltration &
IEM
The treatment of Hyperammonemia aims at restricting the intake of ammonia as well
as increasing its excretion. Physicians make this possible by prescribing pharmacologic
agents like Sodium benzoate and Intravenous Sodium Phenylacetate. These are
commonly used as adjunctive therapy for curing the condition in patients suffering
from deficiency of Urea Cycle Enzyme.
In hyperammonemia ammonia directly affects the CNS .The role of the neurologist is
to provide a basic status evaluation for later reference during follow-up care.
This evaluation is especially useful in the primary genetic entities, in which recurrence
is a virtual certainty and the risk of additional nervous system compromise exists.
MANAGEMENT :
People suffering from chronic disorders are at a life-long risk of suffering from
Hyperammonemia episodes. For such patients, management involves long-time follow
up and monitoring of the ammonia levels. A multidisciplinary approach, involving
Genetic, Dietary, Metabolic, Pediatric and Neurological factors, needs to be followed
for this disease. Specific supportive plans need to be used for dealing with acute
episodes. Therapies used for this disorder need to focus on controlling the symptoms
and avoiding its acute episodes.
1. Biochemistry by U.Satyanarayana and U.Chakrapani

2. Biochemistry by Nelson cox - Leninger

1. http://www.ncbi.nlm.nih.gov/sites/ga?disorder=Hyperammonemia