Male hemizygotes usually present in infancy, while female heterozygotes may be totally asymptomatic. [path.upmc.edu]

Later in life, the disease may present in both males and females. In the classic presentation, a male infant appears well initially, but by the second day of life becomes irritable, lethargic, and stops feeding. [en.wikipedia.org]

Male and female infant or childhood presentations have been reported with vomiting, irritability, and failure to thrive, often triggered by illnesses. [clinicaladvisor.com]

The clinical presentation of OTCD is very heterogeneous. [ojrd.biomedcentral.com]

Rarely, OAT-deficient neonates present with hyperammonaemic encephalopathy due to impaired urea cycle function caused by substrate limitation, with associated hypoargininaemia and hypoornithinaemia. [jhu.pure.elsevier.com]

• Developmental Delay

  […] transporter SLC7A7 (14q11.2)* Biochemical profile: Elevated urine lysine, ornithine, and arginine Clinical features: Protein intolerance, episodic hyperammonemia, growth and developmental delay, diarrhea, vomiting, hepatomegaly, cirrhosis, leucopenia [merckmanuals.com]

  Complications from ornithine transcarbamylase deficiency may include developmental delay and intellectual disability. Ornithine transcarbamylase deficiency is believed to occur in approximately 1 in every 80,000 people. [raredr.com]

  Some children with ornithine transcarbamylase deficiency (OTC) have developmental delays. [babysfirsttest.org]

  Complications from ornithine transcarbamylase deficiency may include developmental delay and mental retardation. Progressive liver damage, skin lesions, and brittle hair may also be seen. [house.wikia.com]

  Less severe mutations cause milder illness, which presents later in life with developmental delay, episodes of metabolic decompensation, seizures, and ataxia. [neuropathology-web.org]

• Hypothermia

  Affected boys are normal at birth but soon after birth they develop acute neonatal encephalopathy with hyperventilation and hypothermia. [centogene.com]

  […] a urea cycle defect reflect those of hyperammonemic encephalopathy (brain edema, metabolic dysregulation and neurotransmitter disturbance), with the exception of ARG deficiency General: Poor feeding, lethargy, behavioral changes Vital Sign Changes: Hypothermia [pedclerk.bsd.uchicago.edu]

  They may rapidly progress to respiratory alkalosis as ammonia increases with cerebral edema, seizures, loss of reflexes, hypothermia, apnea, and coma. [clinicaladvisor.com]

  Infants with a severe urea cycle disorder are normal at birth but rapidly develop cerebral edema and the related signs of lethargy, anorexia, hyper- or hypoventilation, hypothermia, seizures, neurologic posturing, and coma. [themedicalbiochemistrypage.org]

  Clinical Presentation of an Acute Hyperammonemic Episode Poor feeding Lethargy Tachypnea Hypothermia Irritability Vomiting Ataxia Seizures Hepatomegaly Coma Hyperammonemic crises in neonates or infants with OTC deficiency are frequently precipitated by [newenglandconsortium.org]

• Fatigue

  Symptoms of hemolytic anemia may include dark urine, enlarged spleen, fatigue, pale complexion, rapid heartbeat, shortness of breath and yellow skin or eyes (jaundice). [lvhn.org]

  Some FTTDCD patients have growth retardation, hypoglycemia, hyperlipidemia, pancreatitis, fatty liver, hepatoma, and fatigue. [themedicalbiochemistrypage.org]

• Diarrhea

  (dibasic aminoaciduria II; 222700) Dibasic amino acid transporter SLC7A7 (14q11.2)* Biochemical profile: Elevated urine lysine, ornithine, and arginine Clinical features: Protein intolerance, episodic hyperammonemia, growth and developmental delay, diarrhea [merckmanuals.com]

  Symptoms of adrenal dysfunction typically includes muscle weakness and fatigue, weight loss and decreased appetite, darkening of the skin, low blood pressure, fainting, cravings for salt, low blood sugar levels, irritability, depression, diarrhea, nausea [lvhn.org]

• Hypertension

  (PMID: 19138872) Shchelochkov OA … Wong LJ (Molecular genetics and metabolism 2009) 3 22 45 60 Association of ornithine transcarbamylase gene polymorphisms with hypertension and coronary artery vasomotion. [genecards.org]

  Patients have hypertension (high blood pressure). Patients have more than 100 milligrams of sugar per deciliter of blood. Treatment : Patients may receive cholesterol-lowering drugs and anti-hypertensive drugs to lower blood pressure. [lvhn.org]

• Liver Dysfunction

  In NICCD children younger than age one year exhibit growth retardation with transient intrahepatic cholestasis, hepatomegaly, diffuse fatty liver and parenchymal cellular infiltration associated with hepatic fibrosis, variable liver dysfunction, hypoproteinemia [themedicalbiochemistrypage.org]

  Affected individuals may present chronic neurocognitive deficits and liver dysfunction, as well as acute encephalopathy that is secondary to hyperammonemic crisis and may have been precipitated by a variety of factors. [invitae.com]

• Muscle Spasticity

  Unfortunately, even with treatment, some children may experience learning disabilities, intellectual disabilities, or tight muscles (spasticity), which are commonly associated with OTC.Children who do not receive treatment for OTC are at risk for severe [babysfirsttest.org]

• Abnormal Behavior

  Psychiatric symptoms were the primary presenting factors in 21% of the cases and involved abnormal behavior and confused states with hallucinations over time and disorientations in space. [ojrd.biomedcentral.com]

• Seizure

  Signs and symptoms of this form may include lack of energy and appetite, poorly-controlled breathing rate and body temperature, unusual body movements, seizures, or coma. [rarediseases.info.nih.gov]

  The presenting features included delayed psychomotor and language development and occasional seizures. [mhmedical.com]

  Elevated ornithine and glutamine, decreased citrulline and arginine, markedly increased urine orotate Clinical features: In males, recurrent vomiting, irritability, lethargy, hyperammonemic coma, cerebral edema, spasticity, intellectual disability, seizures [merckmanuals.com]

  الصفحة 53 - Neurological abnormalities are prominent, including severe hypotonia, areflexia, poor suck rellex and seizures. Neuronal migration defects may be observed on neuroimaging. [books.google.com]

  In late-onset otc deficiency the symptoms appear from 2 months to 44 years with normal appearance at birth, followed by irritability, vomiting, lethargy, seizures, delayed development, ataxia, and seizures. [icd10data.com]

• Somnolence

  Initial signs include somnolence and poor feeding, usually followed by vomiting, lethargy, and coma central. [path.upmc.edu]

  Signs and symptoms Hyperammonemia from OTC deficiency can be manifested clinically by some or all of the following: Anorexia Irritability Heavy or rapid breathing Lethargy Vomiting Disorientation Somnolence Asterixis (rare) Combativeness Obtundation Coma [emedicine.medscape.com]

  The most common presentation of these defects is in newborns who typically present with somnolence, poor feeding, hyperventilation, and seizures, followed by lethargy and coma [ 3 ]. [jintensivecare.biomedcentral.com]

• Convulsions

  Manifestations of CTLN2 are recurrent hyperammonemia with neuropsychiatric symptoms including nocturnal delirium, aggression, irritability, hyperactivity, delusions, disorientation, restlessness, drowsiness, loss of memory, flapping tremor, convulsive [themedicalbiochemistrypage.org]

  Hepatic Coma (Acquired Hyperammonemia) Portal systemic Encephalopathy / Hepatic encephalopathy Hepatic failure –finally lead to hepatic coma and death Hyperammonemia – characteristic feature of liver failure C/F - Altered sensorium, convulsions, ascites [slideshare.net]

Normal liver and kidney function in most cases, unless hypoxia or shock supervenes Elevated ornithine, glutamine, and alanine levels and relatively low citrulline levels Elevated urinary orotic acid level (may also detect asymptomatic carriers) See Workup [emedicine.medscape.com]

Most of these heterozygous female patients (approximately 80% in the literature) are apparently asymptomatic and present a normal biochemical workup (notably, ammonemia and plasma glutamine). [ojrd.biomedcentral.com]

• Hyperammonemia

  Individuals with OTC deficiency will exhibit symptoms similar to other urea cycle disorders with hyperammonemia. [clinicaladvisor.com]

  Hyperammonemia usually is seen late in the course of severe hepatocellular damage (1). [path.upmc.edu]

  In the hyperornithinemia, hyperammonemia, and homocitrullinuria (HHH) syndrome there is a wide spectrum of clinical manifestations, most of which are related to the toxicity of hyperammonemia. [link.springer.com]

  Type 1 Excludes hyperammonemia-hyperornithinemia-homocitrullinemia syndrome E72.4 transient hyperammonemia of newborn ( P74.6 ) ornithine transcarbamylase deficiency E72.4 ornithine metabolism E72.4 Disturbance (s) - see also Disease metabolism E88.9 [icd10data.com]

  Hyperammonemia Hyperornithinemia Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome Ornithine aminotransferase deficiency Ornithine carbamoyltransferase deficiency References to Index of Diseases and Injuries The code E72.4 has the following [healthprovidersdata.com]

Biochemistry of Ornithine Transcarbamylase Deficiency and Its Treatment. [nejm.org]

There is currently one approved treatment for ornithine transcarbamylase deficiency. [raredr.com]

Inborn Metabolic Diseases: Diagnosis and Treatment. Springer Berlin Heidelberg, 2012. p. 323-332. [jhu.pure.elsevier.com]

TREATMENT Treatment is directed toward preventing increased ammonia production through a protein-restricted diet, avoidance of catabolic states and supplementation of citrulline. [obgynkey.com]

Treatment UCDs are life-threatening. Don’t wait to get treatment. A team of health professionals will care for your child. [webmd.com]

Prognosis With early diagnosis and appropriate therapy the prognosis is good, but because the disorder is mild, diagnostic delay is common and some neurological damage may be sustained. [orpha.net]

Prognosis is less clear in cases of adult onset OTCD, as detection of the disease is almost universally post symptomatic [2]. [house.wikia.com]

Prenatal diagnosis is possible by molecular testsing Repeatedly reinforcing the parents in their abilities to perceive early signs of hyperammonemia and to take immediate steps to obtain medical care can be life saving.(5) Prognosis: Prognosis for older [path.upmc.edu]

[…] patients will often present with headaches, nausea, vomiting, delirium, erratic behavior, or seizures. [2] A detailed dietary history of an affected individual with undiagnosed OTC deficiency will often reveal a history of protein avoidance. [4] The prognosis [en.wikipedia.org]

Women and children who are mildly affected can have an excellent prognosis with proper care. [emedicine.medscape.com]

Etiology MSUD is due to mutations in genes encoding 3 of the 4 subunits of the branched chain 2-ketoacid dehydrogenase (BCKAD) complex. [orpha.net]

Figure 1: Diagram of the urea cycle. http://en.wikipedia.org/wiki/Urea_cycle#mediaviewer/File:Urea_cycle.svg Etiology of Urea Cycle Defects Urea cycle defects result from a deficiency or total absence of the activity of any of the enzymes along the pathway [pedclerk.bsd.uchicago.edu]

Biopsy of the liver shows enlarged hepatocytes, which may over time progress to fibrosis, the etiology of which is unclear. [namrata.co]

The etiology of the encephalopathy was not suspected until hyperammonemia (137 μ/L) was observed. Lactulose treatment produced no improvement in clinical signs, and the patient remained in a deep coma, with ammonia levels elevated up to 254 μ/L. [jintensivecare.biomedcentral.com]

Summary Epidemiology The estimated birth prevalence of MSUD is 1/ 150,000. Around 30% of cases are believed to be of the intermediate type. [orpha.net]

Genatlas disease for OTC Gene neonatal distress and hyperammonemia,including late-onset hyperammonemic coma Relevant External Links for OTC Genetic Association Database (GAD) OTC Human Genome Epidemiology (HuGE) Navigator OTC Atlas of Genetics and Cytogenetics [genecards.org]

Epidemiology: The estimated incidence of 1:80,000 live births may be an underestimation because late onset cases may go undetected. In older individuals, the initial onset can occur at any age up to 40-50 years and beyond. [path.upmc.edu]

Table 1 Epidemiological characteristics of the patients Number of cases 27 52 11 Males 22 21 5 females 5 31 6 Number of deceased 20 7 1 at diagnosis 13 5 1 during follow up 7 2 0 Number of decompensations per patient (and relative to mean length of follow-up [ojrd.biomedcentral.com]

[…] administration of allopurinol or a protein load to identify OTC carriers Genetics Test Information Provides information that may help with selection of the correct genetic test or proper submission of the test request Clinical Information Discusses physiology, pathophysiology [mayomedicallaboratories.com]

Pathophysiologically, OAT catalyzes the conversion of ornithine to Δ 1 -pyrroline-5-carboxylate (P5C). Normally the reaction equilibrium is directed toward the production of P5C. [obgynkey.com]

Although hyperammonemia is the primary cause of mortality and morbidity in these disorders, some of them point to unrelated pathophysiological processes. [news-medical.net]

FINAL DIAGNOSIS: PARTIAL ORNITHINE TRANSCARBAMYLASE (OTC) DEFICIENCY Pathophysiology: OTC deficiency is the most common of the urea cycle disorders (UCD).(1). [path.upmc.edu]

To deal with these types of cases, physicians need to understand the principles of the pathophysiology of ammonia metabolism and how to treat these patients in the intensive care setting. [jintensivecare.biomedcentral.com]

Liver transplantation cannot cure brain damage which has already occurred, but it will prevent future hyperammonemic episodes and prevent further damage. [1] References [ edit ] ^ a b c d e f Wraith, J. E. (2001). [en.wikipedia.org]

Rapid control of the hyperammonemia is crucial in preventing or lessening the degree of mental retardation. [newenglandconsortium.org]

Ammonia toxicity and its prevention. Diabetes, Obesity and Metabolism 2009; 11: 823-835. Wilcken B. Problems in the management of urea cycle disorders. Mol Genet Metab 2004; 81: S86-S91. Back to Table of Contents [pedclerk.bsd.uchicago.edu]

Is chronic lung disease in low birth weight infants preventable? A survey of eight centers. ‎ Página 84 - Tanner JM, Whitehouse RH, Marubini E, Resele LF. The adolescent growth spurt of boys and girls of the Harpenden growth study. ‎ [books.google.es]

As with most inherited diseases, there is no way to prevent these disorders. Teamwork between parents, the affected child, and doctors can help prevent severe illness. [medlineplus.gov]