Neurological Implications of Urea Cycle Disorders

Article 1. Gropman A., Summar M., & Leonard J. Neurological implications of urea cycle disorders


Urea cycle disorders are inclusive of both transporter deficiencies and enzymes that cause resultant hyperammonemia and impaired removal of waste nitrogen. The general incidence of this disorder is approximated to be at the minimum of 1 out of 25000 (Gropman, Summar& Leonard, 2007). It constitutes a group of very uncommon congenital disorders that are as a result of enzymes deficiencies. As a result of the enzyme deficiencies, people who suffer from UCDs have a limited ability to metabolize ammonia. Since they cannot metabolize ammonia, it accumulates in their body. The availability of hyperammonemia in the bodies of the affected individuals brings a lot of effects on the neurological functioning of a person. The most common enzyme deficiencies are ornithine transcarbamylase deficiency and carbamyl-phosphate synthetase deficiency 1. These deficiencies are associated with higher acute neurological injury risks.

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The enzyme deficiencies present in Urea Cycle Disorders can cause cerebral damage. It can also bring a wide clinical spectrum moving from asymptomatic to severe health risks..The main effect of this disorder is hyperammonemia which in return leads to dysfunction of the central nervous system with changes in mental status, seizures, coma, edema and sometimes potential death. As a result, these are the reason why the first articles were written. It has a lot of effects to the affected individual and looking into it was a necessary call.


There are very many methods used for the clinical evaluation of the brain function and the neurological injury degree. These methods are helpful in the provision of prognostic information. The listed below are some of the methods that have use in the clinical evaluation after UCDs.


Neuroimaging is a research and diagnostic tool that can be used give the necessary information about the extent, timing, possible mechanism and reversibility of neural injury in a manner that is most likely noninvasive. The Magnetic Resonance Imaging is a technique that is well established that allows for structural and anatomical imaging that is helpful in the diagnosis, patient management and treatment (Gropman et al., 2007). In UCDs, the adult patients who have partial deficiencies may show reversible signal abnormalities. The brain injury types that are always detected in Urea Cycle Disorders normally vary. However, there are four main that may be detected. The first type is normally characterized by extreme cerebral edema that is normally associated with diffuse atrophy. The second type is characterized by an abnormality that is more like infarct; the third type is characterized by presumably ischemic lesions. These lesions usually are found in the boundary zones of the cerebral intravascular and lastly the fourth type is characterized by symmetric cortical found in the temporal lobes.

Results and discussions

In most people with UCDs, different parts of their brains have different sensitivities and therefore they react differently to the damages caused. The effects that UCD has on an individual are associated with their age which in return has effects on the findings of a brain MRI. People with mild hyperammonemia compared to those who have severe hyperammonemia suffer lesser damages on their brains. They usually suffer very limited or no long term effects of urea cycle disorder. On the other hand, severe episodes of hyperammonemia lead to more spread of neurological damage, have more neurological consequences and have effects on more resistant areas. In a brain MRI, these abnormalities reflect on how the brain involvement is distributed more so in the acute settings. It indicates the involvement within 3-5 days and can be helpful in the determination of neurological outcomes.


The main effects of urea cycle disorders are neurological. Most cases, it is usually related to the effects of hyperammonemia. However, it is not clear enough if ammonia is solely responsible for the signs shown. Hyperammonemia causes cognitive and behavioral changes and presumed energy failure. Samples of the abnormalities of a brain MRI showed how severe the neurological outcomes were. From what we observed, the neurological sequelae severity first increased at the peri-insular region then extended to the frontal, temporal, parietal and lastly it went to the occipital lobes. If the abnormalities in the brain are recognized early, it can be a very useful tool in prognosis assessment and helping the involved clinicians in making treatment decisions. If it is recognized early, those individuals who suffer from the disease can have higher chances of being treated fully.

Article 2. Susan E., David C. Biochemical markers and neuropsychological functioning in distal urea cycle disorders


High levels of plasma ammonia cause high levels of glutamine in both the central nervous system and the plasma. UCD is found to have a big phenotypical spectrum. In cases of neonatal onset diseases, the affected individual usually has a virtually complete deficiency of the enzyme (Susan et al., 2017). This may result to extreme neurological sequelae and hyperammonemia. However, in both adult and childhood forms there are always partial enzyme deficiency which is accompanied with variable symptoms. There is no straightforward neurological outcome prediction at the present. It is so because there is no relation between age of onset, genotype, imaging, phenotype and peak ammonia level. However, generally, duration, age of onset and the degree of hyperammonemia can be used in the prediction of prognosis and how far the neurological changes can be reversed.


We found out that most patterns from brain MRIs related more with urea cycle disorders and if we looked into it, it would help in treating and diagnosing early cases of UCD. Therefore, it was decided that brain MRIs be performed in children so that they could be examined and the cases of abnormalities be checked.


Magnetic resonance spectroscopy

These investigations are usually done so that the chemistry of the brain can be studied: therefore, getting the required information about the disease (Susan et al., 2017). The use of MRS has been helpful in the determination of impaired metabolism. Preliminary experiences indicate that the decrease in myoinositol can be an early preparation for impaired handling of nitrogen in patients. The perfect and preferred MRS data analysis method is absolute metabolite quantitation. It is so because metabolite ratios may flaw by the conclusion that creatine always remains stable at this particular point. Creatine is usually used for taking metabolite measures in magnetic resonance that are normally gotten with a very long echo time. The MRS studies show that monitoring the available -proton in glutamine can be extremely helpful for metabolic control assessment.


In both urea cycle disorder and brain injury, Magnetic resonance spectroscopy has demonstrated the presence of elevated glutamate. In those children who survived urea cycle disorder, there was presence of restricted diffusion in their thalami. However in another patient, she needed extracorporeal membrane oxygenation (Birley., et al., 2011). She also required pressors for her profound and severe hypotension. In her case, there are higher chances that hypotension had contributed to the abnormalities in her Magnetic Resonance Imaging. It is however fortunate that not all children who were imaged were found to be hyperammonemic. Another patient had an MRI abnormality and his abnormality was bilateral. There was only one child who had no abnormality sign on his brain MRI.


Magnetic resonance spectroscopy is very helpful in the determination of abnormalities in brains and impaired metabolism. If done early, it can prevent a patient from suffering the severe consequences of UCD. Both MRS and MRI help in saving the lives of people because they help in recognizing immature abnormalities in the brain of the patient. If the abnormalities are recognized early, it helps in the medical decision making on what is best for the patient. If the abnormalities in the brain are recognized early, it can be a very useful tool in prognosis assessment and helping the involved clinicians in making treatment decisions.

Article 3. Gregory M. Enns. Neurologic Damage and Neurocognitive Dysfunction in Urea Cycle Disorders

The associations between performance and biomarkers on every neuropsychological test are usually determined via Pearson analysis. It is important to do this test separately for every disorder. Historically, a good number of children born with UCD die as neonates. However, there are those who are lucky enough to survive. Prolonged survival of the patient and clinical outcome has been noticed to occur after the patient has used alternative pathway therapy. Regardless of improved survival, in most cases, the developmental outcomes have remained suboptimal (Gregory &Enns, 2008).

Future work discussion

To reduce these cases in future, it is important to rapidly identify and make use of therapy. It is therapy that is making it possible for people with UCD to survive. People should make use of expanded newborn screening to determine these cases as early as possible. If this is done, there will be reduced cases of death in future.


Gregory M. Enns, MB, ChB., (2008). Neurologic Damage and Neurocognitive Dysfunction in Urea Cycle Disorders.Seminars in Pediatric Neurology.

Gropman A., Summar M., & Leonard J., (2007). Neurological implications of urea cycle disorders. SSIEM and Springer 2007.

Susan E., David C., et al., (2017). Biochemical markers and neuropsychological functioning in distal urea cycle disorders.Received: 21 August 2017 / Revised: 29 November 2017 /Accepted: 28 December 2017 /Published online: 8 February 2018.

William R., Johan L., et al., (2011). Urea cycle disorders: brain MRI and neurological outcome.Springer-Verlag 2011