Urea cycle disorder that leads to hyperammonemia and
neurologic symptoms, which are less severe than in other forms of urea cycle
Arginase Deficiency; Hyperargininemia; ARG1 Deficiency.
Unknown. No sexual predilection.
Autosomal recessive. Numerous mutations have
been mapped to 6q23.
The hepatic urea cycle is the major pathway for
metabolism and elimination of proteins and amino acids. Arginase is the
mediator of the terminal step in the urea cycle, explaining the relatively
mild clinical expression of the disease. Multiple allelic variants exist.
The two isoenzymes of arginase—arginase-I (found in the liver) and
arginase-II (located in the kidneys)—are specified by separate gene loci,
called ARG1 (located on 6q23) and ARG2 (on 14q24.1-q24.3). The arginase-I
isoenzyme contributes 98% of the arginase activity in the liver, and its
absence is the cause of argininemia. Isoenzyme type II is inducible, and its
activity may increase up to fourfold in patients suffering from argininemia.
Arginase-II is used to metabolize arginine (released from hepatocytes) to
produce urea and ornithine. While this urea is excreted, the newly
synthesized ornithine returns to the liver and is incorporated in the urea
cycle. Hyperammonemia in arginase deficiency can be severe but most often is
mild to moderate because arginase-II can take over a certain degree of
arginase-I function and because arginine (containing two nitrogen molecules)
still can be released by the liver and then cleared by the kidneys. The
first reason is that formed arginine, which contains two waste nitrogen
molecules, can be released from the hepatocyte and excreted in urine.
Generally based on clinical findings of delayed
development, protein intolerance, and spasticity. However, these symptoms
are unspecific, and the diagnosis may be difficult and missed for a
significant period of time. Diagnosis is confirmed by a red cell arginase
assay. Prenatal diagnosis is possible using DNA analysis.
Onset typically is during the neonatal period.
Main features include failure to thrive, signs of hyperammonemia (anorexia,
irritability, tachypnea, lethargy, vomiting), and additional neurologic
signs (progressive spastic quadriplegia, seizures, mental retardation,
hyperactivity). Coma and cerebral edema may occur. Usually mild hepatomegaly
can occur. Laboratory findings include hyperammonemia, hyperarginemia,
di-amino-aciduria (arginuria, lysinuria, cystinuria, ornithinuria),
oroticaciduria, pyrimidinuria, and elevated amino acid levels in the
cerebrospinal fluid (arginine, ornithine, aspartate, threonine, glycine,
methionine). Stress and infection can trigger an attack.
Assess neurologic function and
review the electroencephalogram. Check liver function (clinically and with
laboratory investigations such as transaminases, γ-glutamyltransferase, bilirubin levels, coagulation tests, proteins). Check
for signs of hypovolemia in case of recurrent vomiting; check electrolytes.
Perioperative nutrition should aim for
high carbohydrate intake and low protein intake to prevent arginine load. To
prevent a catabolic state, avoid longer fasting periods and/or cover them
with dextrose-containing intravenous solutions. Prevent oral, pharyngeal,
and gastrointestinal bleeding (because of risk of hyperammonemia from
absorption of blood) and consider a nasogastric tube for aspiration and
Consider interactions ...