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Ornithine-carbamyl transferase, deficiency in
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(OCT deficiency)
Rare: incidence estimated at 1/40,000 to 1/80,000. X-linked transmission of a mutation of the OCT gene (Xp21.1). Complete enzymatic deficiency in hemizygous boys ( neonatal hyperammoniemic coma, often fatal). Severity is variable among girls, depending on the degree of inactivation of transferred pathologic X. Anomaly of the urea cycle, located mainly in the periportal hepatocytes and in the gut: it is a cascade of enzymatic reactions the goal of which is to transform NH4 into urea eliminated by urine.
Clinical signs vary: metabolic coma, neurologic symptoms (convulsions, focal signs), hepatic (hepatomegaly, cytolysis, hepatocellular failure) or neuropsychiatric signs (ataxia, behavioral disorders). They vary also according to the age of onset of the first symptoms.
- neonatal period: hyperammonemia with vomiting, lethargy or irritability;
- infant: anorexia, vomiting, developmental delay, hepatomegaly. A digestive cause is often searched for before the diagnosis is made;
- childhood and adolescence: clinical picture of acute encephalopathy (Reye syndrome) in a context of stress (fever, protein catabolism, postoperative catabolism) or valproate intake (Depakine) or progressive neurological deterioration (mental retardation, seizures, ataxia). Corticotherapy (increased protein catabolism) or an asparaginase-based chimiotherapy may also be a precipitating factor.
- the postpartum period is also a risk period for a decompensation due to the catabolic reaction induced by uterine involution.
The diagnosis is sometimes made during a brutal decompensation during an infectious episode (pseudo Reye syndrome).
Basic principle of treatment: prevention of hyperammonemia by a low protein diet (protein content is adapted to the age to account for growth and reduced in case of infection or stress such as surgery to limit protein catabolism and the formation of NH4. Moreover, it is often necessary to add Na benzoate (0.25 g / kg / day), Na phenylbutyrate (0.25 g/kg/day) to stimulate alternative metabolic pathways and decrease the synthesis of NH3, or arginine HCl (0.1 to 0.2 g/kg/day) to promote the formation of urea before the step involving OCT.
Anesthetic implications:
- contact the team usually in charge of the child
- minimize the duration of preoperative fasting: administer an electrolytic glucose-containing (5 %, 10 % or 30 %, according to the glycemia)solution as soon as the fasting period begins; in case of elective surgery, stop or decrease protein 24 to 48 h prior to the procedure and adopt the caloric intake with glucose and lipids;
- empty the stomach to prevent a protein intake through the digestive tract when blood is susceptible to be swallowed (otorhinolaryngology, stomatology);
- special monitoring: NH3 (nl: < 50 µmol/L or 20-80 µg/dL)), glucose;
- provide an anesthesia which decreases the stress response: LRA, morphine, postoperative analgesia of quality; avoid dexamethasone which increases the protein catabolism; cautious use of the anti-nausea as they may hide early signs of encephalopathy.
- add Na benzoate (0.25 g/kg/day), and Na phenylbutyrate (0.25 g/kg/day) to promote alternative metabolic pathways and decrease the synthesis of NH4, and arginine HCl (0.1 to 0.2 g/kg/d) to the IV solutions. Be aware that those these solutions can cause hypokalemia
- in case of hyperammonemia > 3 x the normal: IV glucose 10 or 20%, and a loading dose of Na benzoate (0,25 g/kg) and Na phenylbutyrate (0, 25 g/kg), arginine HCl (0.2 g/kg) and carnitine (0.2 mg/kg/day);
- in case of failure of theabove medical treatment: hemofiltration or peritoneal dialysis
References :
Updated: July 2023