• Journal of The Korean Society of Inherited Metabolic disease
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• v.22 no.1
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• pp.15-20
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• 2022

The most common urea cycle disorder is ornithine transcarbamylase deficiency. More than 80 percent of patients with symptomatic ornithine transcarbamylase deficiency are late-onset, which can present various phenotypes from infancy to adulthood. With no regards to the severity of the disease, characteristic fluctuating courses due to hyperammonemia may develop unexpectedly, and can be precipitated by various metabolic stressors. Late-onset ornithine transcarbamylase deficiency is not merely related to a type of genetic variation, but also to the complex relationship between genetic and environmental factors that result in hyperammonemia; therefore, it is difficult to predict the prevalence of neurological symptoms in late-onset ornithine transcarbamylase deficiency. Most common acute neurological manifestations include psychological changes, seizures, cerebral edema, and death; subacute neurological manifestations include developmental delays, learning disabilities, intellectual disabilities, attention-deficit/hyperactivity disorder, executive function deficits, and emotional and behavioral problems. This review aims to increase awareness of late-onset ornithine transcarbamylase deficiency, allowing for an efficient use of biochemical and genetic tests available for diagnosis, ultimately leading to earlier treatment of patients.

• Journal of Yeungnam Medical Science
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• v.24 no.2
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• pp.322-328
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• 2007

Ornithine transcarbamylase (OTC) deficiency is the most common inborn error of urea cycle metabolism; it is inherited in an X-linked manner. The OTC catalyzes the third step of the urea cycle, the conversion of ornithine and carbamyl phosphate to citrulline. Deficiency of OTC leads to the accumulation of ammonia, causing neurological deficits. In most affected hemizygote males, OTC deficiency manifests as hyperammonemic coma that often leads to death in the newborn period, and those who recover from the coma may be neurologically impaired due to the sequelae of the hyperammonemic encephalopathy. In some, late-onset manifestations develop. We report a male neonate with early onset OT deficiency that had apnea and was comatous. On mutation analysis using DNA sequencing after polymerase chain reaction (PCR) amplification of the 10 exons, deletions of 10 bases in codon 285, causing a frame shift was detected in exon 8. The mother and a sister were diagnosed as female carriers. Therefore, genetic counseling and the risk assessment could be provided to the family.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.3 no.1
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• pp.32-37
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• 2003

Ornithine transcarbamylase(OTC) deficiency is the most common of all the urea cycle disorders. In this X-linked disorder, the hemizygote males are more severely affected than heterozygote females. The Heterozygote female may have mild episodic hyperammonemia symptoms in late infancy or childhood(late onset) or no clinical manifestations. Here we report a 6 year-old girl with late onset OTC deficiency who showed recurrent episodic lethargy, mental confusion and ataxia. On mutation analysis using DNA sequencing after PCR amplification of the 10 exons of OTC gene, G to T transversion in codon 221, causing substitution of asparagine for lysine was detected in exon 6.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.16 no.3
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• pp.148-154
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• 2016

A urea cycle disorder is a condition caused by a defect of the enzymes in the urea cycle, and deficiency of ornithine transcarbamylase (OTC), which converts carbamoyl phosphate and ornithine into citrulline, is the most common type of the disorder. OTC deficiency induces the accumulation of precursors of urea, ammonia, and glutamine, leading to neurological symptoms including hypotonia, respiratory failure, seizure, lethargy, and coma and sometimes to death. Because OTC deficiency is inherited in an X-linked manner, typical symptoms such as vomiting, poor feeding, and lethargy appear mainly in male neonates. We recently had a case that presented with neonatal onset lethargy, vomiting, and apnea in a 4-day-old boy. He was diagnosed with OTC deficiency by biochemical phenotype, including hyperammonemia and an increased orotic acid level in the urine. Genetic analysis of the OTC gene showed a novel mutation c.780_781insCAGGCAGTGT (p.Ile261Glnfs*35). He was treated for hyperammonemia using continuous venovenous hemofiltration (CVVH) at 118 hours after birth. After 4 days of CVVH, his consciousness and blood ammonia concentration were normalized, and he was discharged at the age of 53 days. At around 12 months of age, bilateral femur fractures and osteomyelitis occurred in this patient. Two months after the fracture, he died of septic shock, insulin-resistant hyperglycemia, and multi-organ failure.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.15 no.3
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• pp.165-170
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• 2015

Ornithine transcarbamylase (OTC) deficiency is a rare X-linked genetic disorder of urea synthesis in newborns. It is the most common urea cycle disorder and leads to elevated levels of ammonia in the blood. Excessive ammonia can cause various symptoms, including vomiting, lethargy, and coma. Boys have a more serious form of OTC deficiency than girls. If not treated immediately, severe OTC deficiency can lead to neurologic abnormalities, hyperammonemic coma, and death. Because late-onset OTC deficiency, which is more common in girls, presents mild symptoms, it is easy to miss diagnosis and prompt treatment. We describe an 11-month-old girl who presented periodic vomiting, intermittent lethargy, and seizure. She was diagnosed with OTC deficiency by elevated serum ammonia and urine orotic acid levels. Genetic analysis of the OTC gene revealed a missense mutation in exon 5 (c.418G>C). We reported an experience of exact diagnosis and successful treatment of late-onset OTC deficiency in our patient.

• Clinical and Experimental Pediatrics
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• v.54 no.10
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• pp.425-428
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• 2011

Ornithine transcarbamylase (OTC) deficiency is well known as the most common inherited disorder of the urea cycle, and 1 of the most common causes of hyperammonemia in newborns. We experienced a case of a 3-day-old boy with OTC deficiency who appeared healthy in the first 2 days of life but developed lethargy and seizure soon afterwards. His serum ammonia level was measured as > $1,700{\mu}g/dL$ (range, 0 to $45{\mu}g/dL$). Continuous renal replacement therapy (CRRT) in the mode of continuous venovenous hemodiafiltration was immediately applied to correct the raised ammonia level. No seizure occurred after the elevated ammonia level was reduced. Therefore, CRRT should be included as 1 of the treatment modalities for newborns with inborn errors of metabolism, especially hyperammonemia. Here, we report 1 case of successful treatment of hyperammonemia by CRRT in a neonate with OTC deficiency.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.2 no.1
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• pp.72-76
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• 2002

• Journal of The Korean Society of Inherited Metabolic disease
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• v.18 no.2
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• pp.55-61
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• 2018

Orinithine transcarbamylase (OTC) deficiency is the most common inborn error of the urea cycle with resulting hyperammonemia, which is medical emergency in newborns.We recently had a case of a boy that presented with lethargy, seizure, hyperammonemia and hypocalcemia in neonatal period. He was diagnosed with OTC deficiency by two consequent ways which are initial biochemical phenotype including hyperammonemia and an increased orotic acid in his urine and genetic analysis of the OTC gene. The OTC gene showed a novel hemizygous mutation c.913C>T (p.Pro305Ser). He was treated by low protein intake, sodium benzoate, phenylbutyrate sodium, L-arginine, and continuous renal replacement therapy (CRRT). After discharge, he has a relatively good prognosis without notable developmental delay. For good prognosis, the duration of hyperammonemia should be shorten. And it can be reached by an early diagnosis. For early detection of OTC deficiency, targeted exome sequencing will be a important role as well as biochemical tests.

• 대한생식의학회:학술대회논문집
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• 2005.11a
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• pp.110-110
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• 2005

• Journal of Genetic Medicine
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• v.1 no.1
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• pp.5-10
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• 1997

The amino acids formed by degradation of proteins ingested produce ammonia. The ammonia which is broken down and excreted as urea through a process known as the Klebs-Hensleit cycle or the urea cycle (Rezvani, 1995). The urea cycle consists of five enzymes necessary for the synthesis of carbamyl phosphate, citrulline, argininosuccinate, arginine, and urea: carbamyl phosphate synthetase (CPS), ornithine transcarbamylase (OTC), argininosuccinate synthetase (AS), argininosuccinate lyase (AL), and arginase (ARG) (Lloyd, 1992). Congenital deficiencies of the enzymes involved in the urea cycle are diseases that are almost fatal without treatment, showing symptoms like vomiting, lethargy, dyspnea, and coma due to hyperammonemia coming from the accumulation of ammonia and metabolic precursors resulting from the deficiency of one of these enzymes (Batshaw and Brusilow, 1983). Among these, the disease manifested by the congenital deficiency of argininosuccinate synthetase (AS) which is associated with the formation of argininosuccinate in citrulline is called argininosuccinate synthetase deficiency or citrullinemia. There have been two reports on this so far in Korea; one in July 1987 by Kim et al. and the other by Park et al. in 1995. We are to report a case of successful treatment of a child with citrullinemia who was transferred to our hospital due to dyspnea, lethargy, feeding difficulties, convulsions and cyanosis together with some document studies related to this case.