From the Guidelines
The OTC variant c.284T>G is a significant genetic mutation that causes ornithine transcarbamylase (OTC) deficiency, a rare X-linked urea cycle disorder, leading to hyperammonemia and potential neurological damage, and requires immediate medical attention and management with a protein-restricted diet, nitrogen-scavenging medications, and potentially hemodialysis, as recommended by the most recent consensus guidelines 1.
Management of OTC Deficiency
The management of OTC deficiency involves a multi-faceted approach to reduce ammonia levels and prevent neurological damage. This includes:
- A protein-restricted diet (0.5-1.5 g/kg/day) to reduce ammonia production
- Supplementation with essential amino acids to support growth and development
- Nitrogen-scavenging medications such as sodium phenylbutyrate (dose range 250-500 mg/kg/day) or glycerol phenylbutyrate (5.5 mL/m²/day) to help remove excess ammonia
- In some cases, L-citrulline (50-200 mg/kg/day) may be used to help manage the condition
Treatment of Hyperammonemia
During metabolic crises, immediate medical attention is necessary for intravenous therapy, and hemodialysis may be required to rapidly reduce ammonia levels. The choice of dialysis modality depends on various factors, including the patient's clinical status, availability of equipment and staff, and institutional preference 1.
Key Recommendations
- CKRT is the recommended first-line treatment for hyperammonemia when possible, with a blood flow rate (Qb) of 30-50 ml/min and a dialysate flow rate (Qd)/Qb >1.5 1
- Intermittent HD can be used in low-body-weight infants, but may require multiple sessions and can cause hypotension and rapid osmotic shifts 1
- Genetic counseling is important for affected families, as OTC deficiency is an X-linked disorder with variable symptoms depending on X-chromosome inactivation patterns 1
From the Research
Significance of the OTC Variant c.284T>G
There are no research papers to assist in answering this question, as none of the provided studies mention the specific OTC variant c.284T>G.
General Information on OTC Deficiency
- OTC deficiency is a urea cycle disorder that can cause hyperammonemia, leading to encephalopathy and other complications 2, 3, 4.
- The disorder can present at various ages, from neonatal to adult onset 2, 3, 5, 6.
- Treatment for OTC deficiency typically involves a low-protein diet, medications to promote alternative pathways for nitrogen removal, and arginine supplementation 2, 3, 4, 5, 6.
- Hyperammonemic crises can be triggered by various factors, including metabolic stress, febrile illness, fasting, and high protein intake 2, 3, 4, 5, 6.