Rare inherited enzymatic disorder characterized by
severe hyperammonemia. Affected infants clinically present with vomiting,
lack of appetite and failure to thrive, progressive lethargy, severe hypotonia, and coma. This
entity is part of a group of disorders called urea cycle disorders (described later).
Arginosuccinic Aciduria; ASL Deficiency; Arginino
Succinase Deficiency; ASA Deficiency.
Inherited as an autosomal
recessive genetic transmission.
Argininosuccinate lyase is one of six enzymes that
play a role in the metabolism of nitrogen from the body, preventing
accumulation of amino acids from metabolic protein waste and development of
Severity varies among patients. A severe form of
the disorder, characterized by complete absence of the enzyme, usually is present in the
neonatal period and is called the severe form. A milder form of the disorder,
characterized by partial absence of the enzyme, affects infants later during infancy or
early childhood. A late-onset form, which occurs in adults, has been identified.
Hyperammonemia is the main characteristic of this disease. The severe form
of argininosuccinic aciduria occurs 24 to 72 hours after birth, usually
after feeding. This form of the disease is clinically characterized by
refusal to eat, severe failure to thrive, lethargy, vomiting, and neurologic
irritability, often suggesting seizures. Affected infants may experience
respiratory abnormalities, cerebral edema, and hepatomegaly. Hyperammonemic
coma has been reported. If it is left untreated for more than 72 hours,
neurologic abnormalities such as severe developmental delays and mental
retardation are trademarks of surviving infants. Death is always inevitable
for those not treated immediately. In infants with partial enzyme deficiency, onset of the disorder
usually occurs later during infancy or childhood. Clinically, the
symptomatology includes failure to grow and thrive, protein-free diet,
ataxia, lethargy, and vomiting. Other features include dry brittle hair that
may result in alopecia. These infants may alternate between periods of
wellness and hyperammonemia. Hyperammonemic coma and life-threatening
complications are potential complications.
Considerations are several. The children
may require anesthesia while they are in systemic failure. Careful
preoperative assessment of cardiovascular and neurologic status is
important. Acute metabolic encephalopathy, associated with severe cerebral
edema and significant raised intracranial pressure, may be present at
induction. The possibility of subclinical seizure activities during
anesthesia must be considered. Administration of intravenous antiepilepsy
medication should be kept in mind. Severe hepatomegaly and respiratory
abnormalities are among the anesthetic considerations.
Administration of high-calorie
fluid, without protein, must be given preoperatively. The potential risks of
pulmonary aspiration after gastrointestinal surgery may lead to acute
respiratory decompensation because of high protein load. Severe metabolic
acidosis must be treated immediately. The decision to administer general
anesthesia can be made based only on the patient's general health condition.
The most important precautions must be taken to prevent sudden
cardiovascular depression and loss of systemic vascular resistance in
patients already presenting without any systemic reserve.
Urea Cycle Disorders are a group of rare disorders
that affect the urea cycle. The consequence ...