Ornithine transcarbamylase deficiency

Ornithine transcarbamylase deficiency
Other names	OTC deficiency, Ornithine Carbamoyltransferase Deficiency Disease.
Structure of L-Ornithine
Specialty	Medical genetics, metabolic syndrome, pediatrics
Symptoms	Tachypnea, vomiting, lethargy, loss of appetite, early morning headaches, and confusion.[1]
Complications	Liver failure, severe hyperammonemic encephalopathy, coma, death, intellectual, and physical disabilities.[1]
Causes	Genetic mutation.[1]
Diagnostic method	Liver function tests, genetic testing, and a liver biopsy.[1]
Differential diagnosis	urea cycle disorders, fulminant hepatitis, Citrin deficiency, and hyperornithinemia-hyperammonemia-homocitrullinuria syndrome.[2]
Treatment	Hydration, arginine, and hemodialysis.[1]
Prognosis	50% of infants with OTC deficiency die.[1]
Frequency	1 in 14,000 to 1 in 77,000 people.[3]

Ornithine transcarbamylase deficiency also known as OTC deficiency is the most common urea cycle disorder in humans. Ornithine transcarbamylase, the defective enzyme in this disorder, is the final enzyme in the proximal portion of the urea cycle, responsible for converting carbamoyl phosphate and ornithine into citrulline. OTC deficiency is inherited in an X-linked recessive manner, meaning males are more commonly affected than females.

In severely affected individuals, ammonia concentrations increase rapidly causing ataxia, lethargy and death without rapid intervention. OTC deficiency is diagnosed using a combination of clinical findings and biochemical testing, while confirmation is often done using molecular genetics techniques.

Once an individual has been diagnosed, the treatment goal is to avoid precipitating episodes that can cause an increased ammonia concentration. The most common treatment combines a low protein diet with nitrogen scavenging agents. Liver transplant is considered curative for this disease. Experimental trials of gene therapy using adenoviral vectors resulted in the death of one participant, Jesse Gelsinger, and have been discontinued.