urea cycle deficiency ( ucd ) result from defects in the clearance of excess nitrogen produced by the breakdown of protein and other nitrogen - containing molecules . these amino acid products are degraded by hepatic transamination and oxidative deamination to produce ammonia . ammonia is then converted to urea via the five enzymes of urea cycle ( carbamoyl phosphate synthetase , ornithine transcarbamylase , argininosuccinic acid synthetase , argininosuccinase and arginase )   and excreted by the kidneys . any disruption to this nitrogen excretion pathway has the potential to cause hyperammonemia and clinical encephalopathy . ornithine transcarbamylase deficiency ( otcd ) ( omim 311250 ) , an x - linked genetic disorder , is the most commonly inherited ucd . while hemizygous males typically present with hyperammonemic coma in the neonatal period , we present the case of a previously healthy 28-year - old woman who developed neurological cognitive abnormality because of undiagnosed otcd . acute neurological decline and hyperammonemia in previously healthy adults should be investigated and managed with this consideration in mind . our investigation of this patient bears on the potential roles of genetic and environmental factors in the onset of disease expression . we describe a female case of late - onset otcd presenting as severe acute hyperammonemia with coma , successfully treated with arginine , benzoate and hemodialysis . treating this previously healthy antepartum otcd female without delay was very difficult , and we believe this case report could be suggestive and inspire every physician and gastroenterologist . a 28-year - old female visited us with a chief complaint of disturbance of consciousness ( japan coma scale 30 ) . she was confirmed to be pregnant in the 16th week and suffered from hyperemesis gravidarum . however , she began to present mild unconsciousness and this symptom could not be explained by the pregnancy - related hyperemesis . her unconsciousness was progressive , with an elevated plasma ammonia level and a deteriorated japan coma scale value ( table 1 ) . she had no specific past history referring to present illness and she was informed to have no family history . in the first place , we administered glucose , lactulose and kanamycin sulfate to prevent ammonia level from increasing . however , hyperammonemia deteriorated and we had to lower the plasma ammonia level aggressively and started hemodiafiltration ( hdf ) . plasma ammonia was temporally lowered just after hdf , but soon after it was elevated again . we thus began continuous hdf , and thereafter the ammonia level could be hold without rising again and went down gradually . amino acid analysis showed her plasma and urine to be consistent with otcd , allowing us to explain the etiology of hyperammonemia and cognitive and motor disturbance ( table 2 ) . there is one report in the literature of an amino acid substitution at the same site in exon 8 ( 829 c > t , r277w ) which was also associated with late - onset symptoms of otcd . we could follow brain magnetic resonance imaging ( mri ) together with illness state during whole disease period ( fig . 2 ) . a high - signal area in the white matter of the bilateral frontal lobes the ornithine transcarbamylase gene ( otc ) is encoded on the x chromosome and is expressed in the mitochondrial matrix of the small intestine and liver , where it catalyzes the synthesis of citrullin from carbamoyl phosphate and ornithine . otcd has an estimated incidence of 1 in 14,000 and is the only x - linked urea cycle disorder . research on the biochemical and molecular bases of otcd by tuchman et al .   revealed a wide spectrum of genetic defects resulting in different phenotypes . mutations predicted to abolish all enzyme activity were found in the neonatal - onset group , while mutations causing partial or varying enzyme deficiency were found in the late - onset group . patients who were asymptomatic until much later in life were almost always heterozygotes and symptom onset coincided with a precipitating factor such as infection , trauma , sodium valproate , surgery , childbirth or physiological stress [ 6 , 7 ] . otcd is the most common urea cycle disorder leading to hyperammonemia and substantial cognitive and motor deficit . males with latent - onset otcd are not as severely affected but show deficit in executive function such as motor planning and working memory . a broad phenotype is also seen in heterozygous females , with symptoms ranging from behavioral and learning disabilities to protein intolerance , stroke - like episodes and hyperammonemic coma [ 9 , 10 , 11 , 12 , 13 , 14 ] . neurocognitive deficits are a major cause of significant disability in otcd . observed cognitive changes that immediately follow hyperammonemia include decreased mental flexibility , impaired attention , poor planning , problems with working memory and increased impulsivity . in our patient , the results of plasma and urine amino acid analyses were compatible with otcd , allowing us to explain the etiology of her hyperammonemia and neurocognitive deficits . a diagnosis of otcd is confirmed when plasma amino acid analysis shows elevated glutamine and alanine levels and a decreased citrullin level and when orotic acid and uridine are found in the urine . there are no definite guidelines as to when to initiate dialysis in patients with hyperammonemia . however , if a patient presents neurocognitive symptom , high - efficiency hemodialysis should be considered to prevent encephalic damage from advancing . the rapid removal of ammonia by hemodialysis is not associated with disequilibrium syndrome because ammonia is a gas and not osmotically active . he was saved by appropriate therapy in childhood , so his medical history was not considered as an important event by any family member . she had been working as a nurse in a general hospital for 5 years and was not worried at all . as a nurse , she had corresponding medical knowledge , but she did not feel any disability during her job . analyzed 19 adult otcd patients and showed that diffusion tensor imaging is a useful technique that allows identification of white matter tracts invisible by conventional mri and provides a quantitative measure of the microscopic characteristics related to the directional organization of the brain . we consider that simple mri should be useful enough because obvious high - density signals had disappeared 70 days after in our case . our patient had no history of liver function damage and this was her first pregnancy . diagnostic workup revealed hyperammonemia and increased orotic acid levels in urine , as well as an elevated plasma glutamine level and lowered ornithine , citrullin and arginine levels . suspecting ucd , we started further examination . increased nitrogen load of the uterus , placenta and fetus in the antepartum period can partially explain why the urea cycle capability of female otc mutation carriers overloads in the postpartum period . various triggers , such as trauma , infections , surgery , childbirth , parenteral nutrition and the initiation of sodium valproate therapy , have been reported . unfortunately , our patient could not avoid abandoning her baby in order to be saved herself . otcd should be considered in the differential diagnosis of antepartum and postpartum mental status changes in the presence of normal liver function . unknown mutations in other genes can cause phenocopy of otcd . a careful and appropriate treatment of the patient and a multidisciplinary team approach can help prevent brain damage , neurological deficits and death .
ornithine transcarbamylase deficiency ( otcd ) is the most common type urea cycle enzyme deficiencies . 
 this syndrome results from a deficiency of the mitochondrial enzyme ornithine transcarbamylase , which catalyzes the conversion of ornithine and carbamoyl phosphate to citrullin . our case was a 28-year - old female diagnosed with otcd following neurocognitive deficit during her first pregnancy . 
 although hyperammonemia was suspected as the cause of the patient 's mental changes , there was no evidence of chronic liver disease . 
 plasma amino acid and urine organic acid analysis revealed otcd . 
 after combined modality treatment with arginine , sodium benzoate and hemodialysis , the patient 's plasma ammonia level stabilized and her mental status returned to normal . 
 at last she recovered without any damage left .