Symptoms
Neonatal Onset
Infants with urea cycle disorders appear to be healthy newborns at birth. Symptoms
of a urea cycle disorder do not appear until after the infant has ingested protein
through either breast milk or formula. Most infants in the United States are
discharged from the hospital within 24 hours of birth. Typically they still appear
healthy because they have only ingested small amounts of protein up to this time.
In infants with severe defects, symptoms begin to appear within 24-72 hours after birth. The baby has vomiting, may refuse to eat, becomes listless, is difficult to wake up, hyperventilates and eventually will slip into a coma. Physicians often mistake these symptoms as being from a newborn sepsis (infection acquired in the nursery) and will treat the baby with antibiotics.
The earlier the symptoms occur in an infant the more severe the defect. Symptoms within the first five days of life indicate a total blockage in the urea cycle with no protein breakdown occurring. Ornithine Transcarbamylase Deficiency, which occurs only in boys, and Carbamyl Phosphate Synthetase Deficiency that occurs in both sexes, are the most severe because they occur earlier in the urea cycle.
Childhood Onset
Children with milder deficiencies may not be symptomatic in the newborn period.
Because their bodies are growing rapidly they can tolerate higher levels of protein
without becoming ill. They are more likely to become symptomatic as their growth
rates slow down and their protein requirements diminish. It is not uncommon for
these children to have a history of protein avoidance. They avoid eating high
protein foods such as meat, dairy products, and eggs because they make them feel
sick. Irritability, hyperactive behavior, and frequent episodes of vomiting may
precede diagnosis. Concurrent illnesses such as colds and flu, accidents, or
surgeries may trigger a hyperammonemic crisis and lead to stupor and coma.
Adult Onset
Adult onset occurs with milder deficiencies or with female carriers of
Ornithine Transcarbamylase Deficiency. They may have a variety of symptoms including
a history of protein avoidance, vomiting, episodes of unusual behavior, and symptoms
of mental illnesses. Episodes of hyperammonemia are frequently related to illnesses,
accidents, surgeries or high-dose chemotherapy. They do not become acutely ill
until their bodies have high levels of protein breakdown occur. Their partially
functioning urea cycle cannot break down the large volume of protein and excrete
it. It degrades to ammonia and causes the symptoms of hyperammonemia to occur.
Late Onset
Children and adults who present with symptoms have milder deficiencies of the
urea cycle. Symptoms often begin with cyclical vomiting, lethargy, sleep disorders,
delusions, hallucinations, and psychosis. Generally their deficiencies tend to
occur later in the urea cycle and may be incomplete blockages.
References:
6. Summar, Marshall, MD, “ Current strategies for the management of neonatal urea cycle disorders” Journal of Pediatrics, Vol. 128, No. 1, January 2001, p. S30-39.
7. Summar, Marshall, MD and Tuchman, Mendel, MD, “Proceedings of a consensus conference for the managaement of patients with urea cycle disorders” Journal of Pediatrics, Vol. 128, No. 1, p. S6-10.