Ornithine Transcarbamylase (OTC) deficiency is an X-linked disorder that causes high ammonia levels in urea cycle.
It is rare genetic disorder impacts the urea cycle with biochemical process in the liver.
Severe neonatal-onset or late-onset disease affects both genders. OTC enzyme condenses carbamyl phosphate with ornithine to citrulline.
The reduced OTC enzymatic activity causes diminished ammonia incorporation that results in hyperammonemia.
Low-level synthesis in extrahepatic tissues contributes to waste nitrogen disposal.
Cycle activity is regulated by N-acetylglutamate synthesis to activate ammonia incorporation into the cycle. Nitrogen from protein metabolism converts to urea.
Epidemiology
OTC deficiency is the most prevalent disorder occurs in approximately 1 in 14000 to 1 in 80000 live births.
Females with one OTC allele mutation may experience milder symptoms. Late-onset can occur at any age are diagnosed in females but also affects males with partial enzyme activity.
Neonatal-onset OTC deficiency leads to high mortality risks from severe hyperammonemia and long-term neurological impairments.
High morbidity and mortality in neonatal patients require close follow-up with a metabolic centre.
Anatomy
Pathophysiology
Increased hepatic ornithine raises serum levels, whereas excessive mitochondrial carbamoyl phosphate accumulates in the cytosol.
Orotic acid is a key intermediate in the tightly regulated pyrimidine biosynthesis involved in nucleic acids.
Deficiency causes hyperammonemia and accumulation of other toxic metabolites. Hyperammonemia impacts the brain causes symptoms from irritability to coma.
Pyrimidine biosynthesis regulation prevents excessive urinary excretion of orotic acid in healthy humans for nucleic acid synthesis.
Etiology
OTC Deficiency results from mutations in the OTC gene encoding enzyme. This enzyme helps remove excess nitrogen from the body to convert into urea for excretion.
The causes of OTC deficiency are:
Mutation types
Inheritance pattern
X-linked inheritance
Genetics
Prognostic Factors
X-linked trait severity in females varies due to skewed X-inactivation.
Females can be asymptomatic or severely affected by hyperammonemia.
Long-term outlook for OTC deficiency includes guarded expectations for cerebral function.
Prognosis in neonates with hyperammonemic coma depends on hyperammonemia duration.
Heterozygous females seem healthy but show deficits in executive function and fine motor skills.
Clinical History
Clinical History:
Collect details including initial symptoms, triggering factors and medical history to understand clinical history of patient.
OTC deficiency treatment involves protein restriction and ammonia scavengers.
Immediate protein intake cessation is essential for symptomatic OTC deficiency.
Compensatory increases in carbs and lipids prevent muscle amino acid breakdown for energy.
Sodium benzoate, sodium phenylacetate, and arginine require intravenous administration in a monitored large medical facility.
Glycerol phenylbutyrate forms phenylacetate and is noninferior to sodium phenylbutyrate in ammonia control.
»
Home » CAD » Ornithine Transcarbamylase (OTC) Deficiency
Ornithine Transcarbamylase (OTC) Deficiency
Updated :
December 25, 2024
Ornithine Transcarbamylase (OTC) deficiency is an X-linked disorder that causes high ammonia levels in urea cycle.
It is rare genetic disorder impacts the urea cycle with biochemical process in the liver.
Severe neonatal-onset or late-onset disease affects both genders. OTC enzyme condenses carbamyl phosphate with ornithine to citrulline.
The reduced OTC enzymatic activity causes diminished ammonia incorporation that results in hyperammonemia.
Low-level synthesis in extrahepatic tissues contributes to waste nitrogen disposal.
Cycle activity is regulated by N-acetylglutamate synthesis to activate ammonia incorporation into the cycle. Nitrogen from protein metabolism converts to urea.
OTC deficiency is the most prevalent disorder occurs in approximately 1 in 14000 to 1 in 80000 live births.
Females with one OTC allele mutation may experience milder symptoms. Late-onset can occur at any age are diagnosed in females but also affects males with partial enzyme activity.
Neonatal-onset OTC deficiency leads to high mortality risks from severe hyperammonemia and long-term neurological impairments.
High morbidity and mortality in neonatal patients require close follow-up with a metabolic centre.
Increased hepatic ornithine raises serum levels, whereas excessive mitochondrial carbamoyl phosphate accumulates in the cytosol.
Orotic acid is a key intermediate in the tightly regulated pyrimidine biosynthesis involved in nucleic acids.
Deficiency causes hyperammonemia and accumulation of other toxic metabolites. Hyperammonemia impacts the brain causes symptoms from irritability to coma.
Pyrimidine biosynthesis regulation prevents excessive urinary excretion of orotic acid in healthy humans for nucleic acid synthesis.
OTC Deficiency results from mutations in the OTC gene encoding enzyme. This enzyme helps remove excess nitrogen from the body to convert into urea for excretion.
The causes of OTC deficiency are:
Mutation types
Inheritance pattern
X-linked inheritance
X-linked trait severity in females varies due to skewed X-inactivation.
Females can be asymptomatic or severely affected by hyperammonemia.
Long-term outlook for OTC deficiency includes guarded expectations for cerebral function.
Prognosis in neonates with hyperammonemic coma depends on hyperammonemia duration.
Heterozygous females seem healthy but show deficits in executive function and fine motor skills.
Clinical History:
Collect details including initial symptoms, triggering factors and medical history to understand clinical history of patient.
OTC deficiency treatment involves protein restriction and ammonia scavengers.
Immediate protein intake cessation is essential for symptomatic OTC deficiency.
Compensatory increases in carbs and lipids prevent muscle amino acid breakdown for energy.
Sodium benzoate, sodium phenylacetate, and arginine require intravenous administration in a monitored large medical facility.
Glycerol phenylbutyrate forms phenylacetate and is noninferior to sodium phenylbutyrate in ammonia control.
Pediatrics, General
Genetics and Metabolic Disease
Adjust environment for protein-restricted diets with control and clear protein labelling.
Plan and prepare meals to prevent high-protein intake. Maintain hygiene and vaccinations to reduce infection risk.
Avoid strenuous activities without properly monitored. Create emergency plan for hyperammonaemia including medical care and treatment instructions.
Proper awareness about OTC should be provided and its related causes with management strategies.
Appointments with a paediatrician and preventing recurrence of disorder is an ongoing life-long effort.
Pediatrics, General
Glycerol phenylbutyrate:
It is metabolized with ester hydrolysis and pancreatic lipases to phenylbutyrate and phenylacetate.
Arginine:
It enhances production of ornithine to facilitate incorporation of waste nitrogen.
Pediatrics, General
Procedural intervention includes liver transplantation while for acute emergencies dialysis are indicated to manage hyperammonaemia.
Pediatrics, General
In the initial diagnosis phase, the focus is on immediate stabilization of the patient during a life-threatening hyperammonemia crisis.
Pharmacologic therapy is effective in the treatment phase as it includes the use of urea cycle disorder treatment agents.
In supportive care and management phase, patients should receive required attention such as lifestyle modification and interventional therapies.
The regular follow-up visits with the paediatrician are scheduled to check the improvement of patients along with treatment response.
Ornithine Transcarbamylase (OTC) deficiency is an X-linked disorder that causes high ammonia levels in urea cycle.
It is rare genetic disorder impacts the urea cycle with biochemical process in the liver.
Severe neonatal-onset or late-onset disease affects both genders. OTC enzyme condenses carbamyl phosphate with ornithine to citrulline.
The reduced OTC enzymatic activity causes diminished ammonia incorporation that results in hyperammonemia.
Low-level synthesis in extrahepatic tissues contributes to waste nitrogen disposal.
Cycle activity is regulated by N-acetylglutamate synthesis to activate ammonia incorporation into the cycle. Nitrogen from protein metabolism converts to urea.
OTC deficiency is the most prevalent disorder occurs in approximately 1 in 14000 to 1 in 80000 live births.
Females with one OTC allele mutation may experience milder symptoms. Late-onset can occur at any age are diagnosed in females but also affects males with partial enzyme activity.
Neonatal-onset OTC deficiency leads to high mortality risks from severe hyperammonemia and long-term neurological impairments.
High morbidity and mortality in neonatal patients require close follow-up with a metabolic centre.
Increased hepatic ornithine raises serum levels, whereas excessive mitochondrial carbamoyl phosphate accumulates in the cytosol.
Orotic acid is a key intermediate in the tightly regulated pyrimidine biosynthesis involved in nucleic acids.
Deficiency causes hyperammonemia and accumulation of other toxic metabolites. Hyperammonemia impacts the brain causes symptoms from irritability to coma.
Pyrimidine biosynthesis regulation prevents excessive urinary excretion of orotic acid in healthy humans for nucleic acid synthesis.
OTC Deficiency results from mutations in the OTC gene encoding enzyme. This enzyme helps remove excess nitrogen from the body to convert into urea for excretion.
The causes of OTC deficiency are:
Mutation types
Inheritance pattern
X-linked inheritance
X-linked trait severity in females varies due to skewed X-inactivation.
Females can be asymptomatic or severely affected by hyperammonemia.
Long-term outlook for OTC deficiency includes guarded expectations for cerebral function.
Prognosis in neonates with hyperammonemic coma depends on hyperammonemia duration.
Heterozygous females seem healthy but show deficits in executive function and fine motor skills.
Clinical History:
Collect details including initial symptoms, triggering factors and medical history to understand clinical history of patient.
OTC deficiency treatment involves protein restriction and ammonia scavengers.
Immediate protein intake cessation is essential for symptomatic OTC deficiency.
Compensatory increases in carbs and lipids prevent muscle amino acid breakdown for energy.
Sodium benzoate, sodium phenylacetate, and arginine require intravenous administration in a monitored large medical facility.
Glycerol phenylbutyrate forms phenylacetate and is noninferior to sodium phenylbutyrate in ammonia control.
Pediatrics, General
Genetics and Metabolic Disease
Adjust environment for protein-restricted diets with control and clear protein labelling.
Plan and prepare meals to prevent high-protein intake. Maintain hygiene and vaccinations to reduce infection risk.
Avoid strenuous activities without properly monitored. Create emergency plan for hyperammonaemia including medical care and treatment instructions.
Proper awareness about OTC should be provided and its related causes with management strategies.
Appointments with a paediatrician and preventing recurrence of disorder is an ongoing life-long effort.
Pediatrics, General
Glycerol phenylbutyrate:
It is metabolized with ester hydrolysis and pancreatic lipases to phenylbutyrate and phenylacetate.
Arginine:
It enhances production of ornithine to facilitate incorporation of waste nitrogen.
Pediatrics, General
Procedural intervention includes liver transplantation while for acute emergencies dialysis are indicated to manage hyperammonaemia.
Pediatrics, General
In the initial diagnosis phase, the focus is on immediate stabilization of the patient during a life-threatening hyperammonemia crisis.
Pharmacologic therapy is effective in the treatment phase as it includes the use of urea cycle disorder treatment agents.
In supportive care and management phase, patients should receive required attention such as lifestyle modification and interventional therapies.
The regular follow-up visits with the paediatrician are scheduled to check the improvement of patients along with treatment response.
Both our subscription plans include Free CME/CPD AMA PRA Category 1 credits.
Digital Certificate PDF
On course completion, you will receive a full-sized presentation quality digital certificate.
medtigo Simulation
A dynamic medical simulation platform designed to train healthcare professionals and students to effectively run code situations through an immersive hands-on experience in a live, interactive 3D environment.
medtigo Points
medtigo points is our unique point redemption system created to award users for interacting on our site. These points can be redeemed for special discounts on the medtigo marketplace as well as towards the membership cost itself.
Community Forum post/reply = 5 points
*Redemption of points can occur only through the medtigo marketplace, courses, or simulation system. Money will not be credited to your bank account. 10 points = $1.
All Your Certificates in One Place
When you have your licenses, certificates and CMEs in one place, it's easier to track your career growth. You can easily share these with hospitals as well, using your medtigo app.
