Disease name: Ornithine Transcarbamylase (OTC) Deficiency

ICD-10 Disease Code: E72.4 - Disorders of ornithine metabolism

ICD-10 Disease Group: E72- Other disorders of amino-acid metabolism

Ornithine transcarbamylase deficiency (OTCD) is an inherited metabolic disorder that causes ammonia to accumulate in the blood. OTCD is caused by genetic variants in the OTC gene that encodes a liver enzyme responsible for detoxification of ammonia. The consequential build-up of excess levels of ammonia in the blood can lead to severe disease symptoms such as cumulative and irreversible neurological damage, coma and death.  OTCD is the most common urea cycle disorder involving various processes that occur in liver cells. The liver processes excess nitrogen that is produced by protein metabolism to make urea that is excreted by the kidneys. The ornithine transcarbamylase enzyme catalyses a specific reaction within this process.

The severe form of the condition is detectable just a few days after birth and is more common in boys than girls and is referred to as the neonatal-onset form. Other forms of the condition may become apparent later in life and may vary in severity. Mutations in OTC that result in complete loss of enzymatic activity result in the severe, neonatal-onset form while mutations leading to decreased OTC activity result in the late-onset phenotypes.

OTCD is an X-linked disorder involving mutations in the OTC gene (Xp21.1) that provides instructions for making the ornithine transcarbamylase enzyme.

The prevalence of OTC deficiency is estimated to range from 1 in 14,000 to 1 in 77,000 people.

Infants with neonatal-onset OTCD may be lacking in energy, unwilling to eat, and have a poorly-controlled breathing rate or body temperature. Infants with this disorder may be described as "floppy" and can experience seizures or coma. Other developmental symptoms may include developmental delay, intellectual disability and progressive liver damage.

Symptoms can vary in severity and onset with some individuals developing symptoms much later in life. The late-onset form of the disorder occurs in both males and females equally and symptoms include mental delirium, erratic behaviour, headaches, vomiting, aversion to proteinaceous foods, and seizures.

Currently there is no cure for OTCD. Treatment may require the coordinated efforts of a team of specialists including paediatricians, neurologists, geneticists, dieticians, and physicians who are experienced in managing metabolic disorders. Occupational, speech and language, and physical therapists may be necessary to treat children with developmental disabilities.

Symptoms may be managed through a combination of dietary restrictions and medications that stimulate the removal of nitrogen from the body. Severe cases may be treated immediately in a tertiary care centre. Long-term management involves life-long restriction of protein intake and nitrogen scavenger therapy. Liver transplantation may also be considered in patients with severe, neonatal-onset OTCD.

• https://www.icd10data.com/
• https://www.orpha.net/consor/cgi-bin/index.php
• https://rarediseases.org/
• https://medlineplus.gov/genetics/
• https://www.cdc.gov/

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Ornithine transcarbamylase (OTC) deficiency