Citrullinemi
a
Type I
Biochemistry II
Nontakorn Kwanmuang
6330073931
General Discussion
Citrullinemia type I (CTLN1) is a rare autosomal recessive
genetic disorder that includes a neonatal acute (classic)
form, a milder late-onset form, a form that begins during or
after pregnancy, and an asymptomatic form.
CTLN1 is caused by deficiency or absence of the enzyme
argininosuccinate synthetase (ASS). ASS is one of six
enzymes that play a role in the removal of nitrogen from
the body, a process known as the urea cycle. The lack of
this enzyme results in excessive accumulation of nitrogen,
in the form of ammonia (hyperammonemia), in the blood
and all body fluids.
2
Infants with the classic form
may experience vomiting,
refusal to eat, progressive
lethargy, and show signs of
increased intracranial
pressure. Prompt treatment
can prolong survival, but
neurologic deficits are
usually present. The course
of the late-onset form is
sometimes milder but
episodes of hyperammonemia
are similar to the classic
form.
3
CTLN1 is
caused by
mutations
in the ASS1
gene that
is
responsible
for
production symptoms of CTLN1 develop
due to deficiency of this
enzyme, which is needed to
detoxify ammonia in the
body. Failure to properly
remove ammonia via
synthesis of urea leads to
the abnormal accumulation
of ammonia in the blood
(hyperammonemia).
Signs and symptoms in babies include:
- Breathing problems - Changes in muscle tone
- Drowsiness - Fussiness
- Little appetite or trouble eating
- Loss of consciousness (passing out)
- Low body temperature - Throwing up - Weak muscles
4
Signs and symptoms
of milder forms of
CTLN1 in babies are
the same as for those
babies with ASA
Treatment
The treatment of CTLN1 is aimed at preventing
excessive ammonia from being formed or for
removing excessive ammonia during a
hyperammonemic episode. Medications that assist
in the removal of nitrogen from the body by
providing an alternative means of waste nitrogen
removal are employed. Available medications are
Buphenyl, Ammonul, and Raviciti, as well as
5
arginine.
Dietary restrictions are aimed at limiting the
amount of protein intake to avoid the development
of excess ammonia. However, enough protein must
be taken in by an affected infant to ensure proper
growth. Infants are placed a low protein, high
calorie diet supplemented by essential amino acids.
A combination of a high biological value natural
protein such as breast milk or cow’s milk formulate,
an essential amino acid formula, and a calorie
supplement without protein is often used.
Multiple vitamins and calcium supplements may
also be used.
6
References
Nevada State Public Health Laboratory. Nevada: Amino
Acid Metabolic Disorders [online]. Available at:
https://med.unr.edu/nsphl/newborn-screening/disorders/a
mino-acid-metabolic-disorders
MedlinePlus. U.S. National Library of Medicine:
Citrullinemia [online]. Available at:
https://medlineplus.gov/genetics/condition/citrullinemia/#
references
NORD National Organizations for Rare Disorders.
Washington: Rare Disease Database, Citrullinemia Type I
[online]. Available at: https://rarediseases.org/rare-
diseases/citrullinemia-type-1/
