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The mysterious world of OTC deficiency: Why can ammonia be fatal?
OTC deficiency (Ornithine transcarbamylase deficiency) is the most common urea cycle disorder in humans. The root cause of this disease is a defect in an enzyme called OTC. This enzyme is responsible for converting amino acids into a form that can be processed by the body. Therefore, when OTC is lacking, the ammonia concentration in the body will rise sharply, which may cause epilepsy, coma or even death. The inheritance of this disease is X-linked recessive, which means that men are much more likely to be affected than women. From this perspective, OTC deficiency and the risks it poses force us to think about the challenges of modern medicine.
Symptoms and manifestations
The symptoms of OTC deficiency vary among individuals, especially in women with the recessive gene. Typically within a few days of birth, a baby boy's initial health deteriorates rapidly due to elevated ammonia levels. This is often accompanied by the following symptoms:
Fever, lethargy, and difficulty eating may eventually worsen to coma or even death.
In late-onset cases, patients' presentations are more diverse, including headaches, nausea, vomiting, and a range of psychiatric symptoms, such as confusion and self-injury. Even mild cases can trigger dangerous hyperammonemia in the face of external stress, making early diagnosis crucial.
Genetic background
OTC deficiency is caused by mutations in the OTC gene located on the X chromosome. This mutation blocks the production of transaminases, which are normally expressed only in the liver. Because it is X-linked recessive inheritance, therefore:
Men are mostly symptomatic, while women may be asymptomatic carriers or show mild symptoms.
Although the number of genetic mutations is small, 15% of patients still develop the disease due to gene deletion. Therefore, early genetic testing is very important for people with a family history of the disease.
Diagnosis process
Urea cycle disorders are one of the differential diagnoses that must be considered when evaluating patients with hyperammonemia. Diagnosing OTC deficiency usually involves the following tests:
Amino acid analysis of plasma and urine, urine organic acid analysis, and mass spectrometry analysis, etc.
These tests can help identify changes that are hallmarks of OTC deficiency, such as decreased citrate and arginine concentrations and increased oxalyl acid. Diagnosis is more challenging for female carriers because changes in blood chemistry tests may not be apparent, and molecular genetic testing is increasingly viewed as a more reliable diagnostic tool.
Treatment Plan
The current main goal in treating OTC deficiency is to avoid ammonia accumulation. This can be prevented beforehand with a low-protein diet and nitrogen scavengers. In an acute episode of hyperammonemia, emergency treatment such as dialysis may be required. With the advancement of medical technology, liver transplantation is regarded as the only option to cure this disease:
After liver transplantation, the patient's five-year survival rate exceeds 90%.
This allows patients with severe OTC deficiency to be considered for transplant evaluation, typically at six months of age.
Prognosis and cultural influences
A 1999 retrospective study showed that 32% of newborns died during their first episode of hyperammonemia. Of those who survive, less than 20% survive to age 14. These tragic cases remind us that raising awareness of this disease is critical.
In modern culture, OTC deficiency has also appeared in episodes of popular television series such as "House, M.D." and "Chicago Med," demonstrating the impact of this rare disease on popular consciousness. However, the complexity and mortality risk of this disease make people wonder: How should we prepare ourselves to face unexpected challenges when faced with unknown diseases?
