Maple Syrup Urine Disease Pathogenesis

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Table of Contents

Introduction
Literature Review
Methodology
Analysis
Discussion
Conclusion
References

Introduction

The maple syrup urine disease is a condition caused by the inability of the body to process certain amino acids. This results in the accumulation of the branched-chain amino acids within the body and the brain. This case report will focus on the causes, symptoms, effects, treatment as well as preventive measures. It will be based on the observations made on patients, an analysis of the symptoms, focusing on the observable and non-physical symptoms that can be observed from laboratory tests.

Many individuals with the conditions were observed over a certain period, and laboratory tests were carried out to establish the causes, symptoms, effects and preventive measures. The case study was done to determine the type of mutation that occurs in the genes of the patients, resulting in this condition. It was also aimed at determining whether this condition is hereditary (Milunsky, 2011).

Literature Review

Various authors have written concerning the MSUD. According to some, this condition is hereditary; hence children from families that have recorded this condition are more likely to be affected, as opposed to those from MSUD-free families. This was determined by checking the accumulation of the amino acids in the plasma of these two categories of children. As per the findings, dietary measures are more effective in controlling this condition. According to Donaldson, cerebral edema and metabolic intoxication are the main effects of this condition. This was established after doing amino acid tests on the blood plasma of the individuals under observation (Donaldson, 2012).

If the condition is controlled, it can ensure near-normal development, and even reduce the rates of hospitalization. This does not, however, prevent neurological deterioration. According to Menkes, individuals suffering from this condition should have effective medical care, a checked diet, and have their plasma amino acid levels monitored. If not well treated, the patient might show signs of hypoglycemia and acute ketoacidosis. An individual’s diet should have less branched-chain amino acid (Shellmer, 2010).

Methodology

The methods used in the collection of the data and information in this case study include primary and secondary sources. The secondary sources used include books, journals, and periodicals on MSUD. The advantage of this method is that the information was readily available. It was less cumbersome and less time-consuming. A detailed analysis of the condition from different authors was readily available, hence enhancing comparison and a deeper understanding of the condition.

The other methods used were primary sources. This involved interviews and observation. Those adults diagnosed with the condition were interviewed concerning some of the observable symptoms that they had. The observation was, however, used during the laboratory tests that were done on the plasma, and the urine of the affected individuals. Primary sources provided firsthand information that was not biased concerning the condition. It however needed more time and was cumbersome.

Laboratory Results

According to the laboratory findings, maple syrup urine disease is characterized by a high concentration of branched-chain amino acid, for instance, valine, within the body. Findings also show that those with the condition tend to have respiratory and neurological problems. It also results in the imbalance of the plasma amino acids within the body. Children with MSUD often show conditions of irritability, poor appetite, and ketonuria. If the condition is severe, one might even go into a coma. According to the observations, children with the condition were prone to poor development, irritability, leucinemia, and dehydration.

Laboratory tests indicated that individuals with this condition were prone to hypoglycemia and hyperammonemia. Analysis of the activity of the branched-chain alpha-ketoacid dehydrogenase indicated that this enzyme was inactive resulting in the accumulation of branched-chain amino acids in the body cells. Laboratory tests also pointed to a higher concentration of branched-chain ketoacids in the urine. Branched-chain alpha-ketoacid dehydrogenase complex mutation often results in the formation of a different phenotype.

If a child is suspected of having MSUD due to the clinical findings, ethnicity, or family background, various tests need to be done to verify the condition. For instance, there is a need to find out whether the cerumen has a maple syrup odor. This has to be done between 12 to 24 hours after birth. For this condition, dietary therapy is the best remedy. Findings show that children with this condition, if not treated promptly are prone to the swelling of their brains, which might lead to the central respiratory system breakdown. It is therefore important to carry out an analysis of the plasma amino acid (Acosta, 2010).

Carriers of MSUD can be identified by checking their disease-causing mutations. Identification of the disease-causing mutation is vital for the prenatal diagnosis of the unborn that are at a higher risk. Individuals with this condition exhibit severe metabolic intoxication.

The well-known types of this condition include the classical MSUD, intermediate MSUD, intermittent and thiamine responsive MSUD. According to the findings, classic MSUD is characterized by ketonuria and high levels of branched-chain amino acid. A similar trend is exhibited by plasma also-isoleucine and the branched-chain ketoacids. The urine also tests positive for DNPH. This level of the condition usually starts at the neonatal stage. The intermediate type of the condition is also characterized by the same biochemical signs exhibited by the classical type of MSUD. This type is however less severe than the classical type.

The intermittent type of the MSUD is, however, characterized by normal levels of branched-chain amino acid when the individual is well. When the individual is unwell, biochemical signs exhibited are similar to those of the classic type. The thiamine responsive type of this condition is characterized by leucine tolerance, and thiamine therapy helps in improving the biochemical condition of the patient (Louis, 2008).

Metabolic Considerations

According to the laboratory tests carried out, individuals with classic MSUD were found to have near-zero leucine oxidation and their loss of branched-chain amino acid through the urine was negligible. It also emerged that individuals with intermediate MSUD had a higher leucine tolerance. They were less prone to significant fluctuations in the branched-chain amino acid than those with classic MSUD. This can be attributed to the existence of BCKAD enzyme activity. They are, therefore, less prone to essential amino acid deficiencies. There is no disparity in the levels of branched-chain amino acids in such individuals, whether they are well or unwell.

Analysis

According to the laboratory tests carried out, it also emerged that individuals with the MSUD experienced severe metabolic crisis only if they had reduced BCKAD enzyme activity. It was clear that those with a higher BCKAD enzyme activity had a higher tolerance to leucine. They, therefore, experienced less metabolic crisis and reduced levels of plasma leucine concentration. It was also realized that the maple syrup odor was quite evident in their urine and cerumen. Irritability and poor appetite were observable in these individuals. They exhibited stereotyped movements, for instance, fencing and cycling. In severe cases, they were prone to coma or experienced respiratory failure.

After the neonatal period, the children with the condition had leucosis due to leucine intoxication. This is precipitated by protein degradation caused by infection, injury, surgery, or stress. Some experienced ataxia, sleep disturbances, mood swings, and hallucinations. Focal dystonia and cognitive impairment were also common in the victims. The main cause of coma in some patients was attributed to the increase in the leucine and alpha-ketoisocaproic acid levels in the plasma. In such a case, the most visible symptoms of the condition were nausea and vomiting (Brodsky, 2010).

Individuals with this condition were at a high risk of cerebral edema and neurological disorders. This can be attributed to leucosis and hyperosmolarity caused by high levels of branched-chain amino acid, keto acid, and high levels of fatty acids in the plasma. The condition is also characterized by an increase in the level of branched-chain keto acids and sodium in the urine. This condition is reversible if there is no significant brain damage to the individual during the earlier stages of brain development. A long-term amino acid imbalance often affects the child’s brain, which might result in neurological damage. Some children with the condition exhibited signs of hyperactivity or impulsivity, accompanied by low concentration levels. In adults, however, increased cases of cognitive impairment were common.

Non-central Nervous System Symptoms of MSUD

Acute deficiency of isoleucine, leucine, and valine, which are essential amino acids, often results in retarded growth, hair loss and anorexia. People with classic MSUD are prone to nutritional deficiencies. They often lack zinc, essential omega-3 fatty acids, as well as selenium and folic acid. From the observations made, it was found out that individuals with classic MSUD had a lower borne density than their peers who did not have the condition. This often resulted in frequent bone fractures, which caused transient leucosis. This condition is referred to as osteoporosis.

Oesophageal candidiasis is also a characteristic of individuals with MSUD. The candida can be attributed to the T-cell inhibitory effect due to high levels of leucine. It might also be due to iatrogenic immunodeficiency that results from the inadequate intake of branched-chain amino acids. Severe pancreatitis is also evident as they are treated for leucine intoxication. The condition emerges when the leucine levels are normalizing (King, 2012).

Discussion

Pathophysiology

Leucine and alpha-ketoisocaproic acid often cause a syndrome that affects the brain protein. It affects the synthesis of neurotransmitters and the growth of neurons. The deficiency of cerebral amino acids severely affects the growth of the brain and causes neurotransmitter deficiency. Alpha-ketoisocaproic acid and other branched-chain keto-acids intoxication often affect the brain and other muscles. The carriers of this condition are common, and it might be as high as one in every ten people in some areas.

Managing the Condition

To determine whether one has the classic or intermediate type, it is important to look at the ratio between branched-chain amino acids, essential as well as non-essential amino acids. Regulated concentration levels usually indicate residual BCKAD enzyme activity. Acute BCKAD enzyme deficiency often affects amino acid homeostasis, which affects the levels of plasma amino acids. In milder forms of MSUD, the concentration levels of plasma branched-chain amino acid might be high, yet the plasma amino acid concentration remains relatively regulated (Nicola, 2011).

Treatment of the Maple Syrup Disease

Home therapy can be administered to those with mild MSUD. Detection of this condition is made possible by the use of the Dinitrophenylhydrazine (DNPH) reagent, which detects high levels of branched-chain keto-acids in the urine. After early detection, dietary therapy can be used which entails leucine restrictions and taking formulas that are free of high-calorie branched-chain amino acids. This should be done by an experienced practitioner. Out-patient monitoring is also vital. In case of severe vomiting, it might be appropriate to seek inpatient services from a qualified medical practitioner (Fernandes, 2006).

Acute decompensation

Diet indiscretion often leads to an increase in plasma branched-chain amino acids. In rare cases, however, it results in severe decompensation. Metabolic decompenation can be corrected by treating or preventing conditions that lead to precipitate stress. Measures must be undertaken to ensure effective protein synthesis, especially in the liver and other body muscles. This is made possible by the administration of insulin, controlling leucine levels by taking the correct measures to alleviate leucine intoxication, ensuring that the patient takes the right calories as well as valine and isoleucine. There is also a need to monitor the levels of plasma amino acids.

Nausea and vomiting can be controlled by the use of antiemetics. There is a need to ensure that the affected individual gets the essential and non-essential amino acids that are free from branched-chain amino acids. In case of a metabolic crisis, the individual must get specific amino acid supplements, like isoleucine and valine as well as glutamine and alanine. There is also a need to control brain edema. Decreased blood osmolarity can be fatal in children, hence the need to control the same. Neurological assessment is vital in monitoring brain edema.

Besides dietary therapy, hemodialysis has been cited as being able to control this condition. Other remedies to the condition include; neuropsychiatric morbidity, Thiamine treatment, liver transplantation and management of pregnancy (Walberg, 2005).

Conclusion

MSUD is a hereditary metabolic disorder that results from the inability to break down certain amino acids. The condition is best treated using dietary therapy. People with this condition have a higher concentration of leucine, which often results in neurological complications. Some of the symptoms of this disorder include; coma, seizures, vomiting, loss of appetite, stunted growth, neurological damage, sleep disorder, and maple syrup scent in the urine.

The four major types of this disorder include the classic, intermediate, intermittent and thiamine responsive types. To test for this condition, a plasma and urine amino acid test are essential. In the treatment of this condition, besides dietary therapy, hemodialysis might help in the reduction of plasma amino acids. The monitoring of the individual’s amino acid is essential in making sure that the nervous system of the patient is not damaged. The individual must be treated for any stressful conditions and other illnesses. With proper treatment, individuals with this condition can live near-normal lives.

References

Acosta, P. (2010). Nutrition Management of Patients with Inherited Metabolic Disorders. Boston: Jones & Bartlett Publishers.

Brodsky, M. (2010). Pediatric Neuro-Ophthalmology. New York: Springer.

Donaldson, I. (2012). Marsden’s Book of Movement Disorders. Oxford: Oxford University Press.

Fernandes, J. (2006). Inborn Metabolic Diseases: Diagnosis and Treatment. London: Springer.

King, M. (2012). Case Study of Maple Syrup Urine Disease. Web.

Louis, D. (2008). Greenfield’s Neuropathology. CRC Press: New York.

Milunsky, A. (2011). Genetic Disorders and the Fetus: Diagnosis, Prevention and Treatment. New York: John Wiley & Sons.

Nicola, L. (2011). Maple syrup urine disease. Web.

Shellmer, D. (2010). Cognitive and Adaptive Functioning after Liver Transplantation for Maple Syrup Urine Disease: A Case Series. Web.

Walberg, S. (2005). Pediatric Nutrition in Chronic Diseases and Developmental Disorders. Oxford: Oxford University Press.

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