Urea Cycle Disorders: Carbamoyl Phosphate Synthetase 1 Deficiency
Carbamoyl phosphate synthetase 1 (CPS1) deficiency is a urea cycle disorder. The urea cycle is extremely important in that it rids the body of nitrogenous waste. CPS1 is the first rate-limiting step in the cycle and it combines ammonia and bicarbonate into carbamoyl phosphate. Carbamoyl phosphate then combines with ornithine to enter the urea cycle.
There are 2 types of CPS1 deficiencies. The primary deficiency, which is due to a mutation of the CPS1 gene; and the secondary deficiency, which is a lack of coenzyme NAG. CPS1 requires NAG to catalyze the entry of ammonia and bicarbonate into the urea cycle. Without NAG, there is a build up of ammonia. When a patient completely lacks the CPS1 gene, symptoms start immediately at birth. These symptoms include refusal to eat, lethargy, lack of appetite, vomiting, and irritability. If the condition goes untreated, the baby can experience seizures, respiratory distress, and abnormal movements. These symptoms are caused by encephalopathy (swelling of the brain) due to hyperammonemia (a build up of ammonia). If the condition continues to go untreated, the baby could slip into coma and end up suffering from neurological damage and/or delayed development.
There are 2 types of CPS1 deficiencies. The primary deficiency, which is due to a mutation of the CPS1 gene; and the secondary deficiency, which is a lack of coenzyme NAG. CPS1 requires NAG to catalyze the entry of ammonia and bicarbonate into the urea cycle. Without NAG, there is a build up of ammonia. When a patient completely lacks the CPS1 gene, symptoms start immediately at birth. These symptoms include refusal to eat, lethargy, lack of appetite, vomiting, and irritability. If the condition goes untreated, the baby can experience seizures, respiratory distress, and abnormal movements. These symptoms are caused by encephalopathy (swelling of the brain) due to hyperammonemia (a build up of ammonia). If the condition continues to go untreated, the baby could slip into coma and end up suffering from neurological damage and/or delayed development.
Some patients have a partial lack of the CPS1 gene. These patients may not experience symptoms until later in childhood or even into adulthood. Symptoms
may include failure to thrive, ataxia, lethargy, vomiting, or hypotonia
(diminished muscle tone)
chronic
encephalopathy, autism, learning disorders, hyperactive and self-injurious
behavior, and usually come about after some sort of illness or catabolic stress. It has also been found that these patients often experienced protein aversion when they were younger.
Dietitians play an important role in this disease in that majority of treatment revolves around diet. The goal is to decrease nitrogen in the diet and ultimately reduce ammonia in the blood. Many patients go on hemodialysis to decrease ammonia levels. A very low protein diet must be followed. This would be about 20-25g of protein per day for adult women, and 20-32g of protein per day for adult men. Patients must be on a hypercaloric diet to prevent catabolism. If a patient experiences an episode of hyperammonemia, they may need to go on a protein-free, hypercaloric diet for 24-48 hours. Many patients will also receive a continuous solution of insulin and dextrose until they are back in an anabolic state. Patients should also avoid large protein loads and space protein intake out throughout the day.
As dietitians I think it would be important for us to monitor diet adherence, as well as creatinine, BUN, and even ketone levels to ensure patients do not go back into a catabolic state. Special meal plans may be required to ensure patients are eating enough calories, carbohydrates, and fats, but keeping protein intake minimal.
Although this disease is rare it is important for healthcare professionals to understand how to treat it when a situation arises. It is also important for healthcare professionals to diagnose the disease properly to avoid life-threatening signs and symptoms.
SR
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