Tyrosinemia Type 1 (Metabolic Disorder) Paper


Generally, tyrosinemia is a genetic disorder indicated by the multistep process that functions to break down amino acid tyrosine. Tyrosine is a constituent of many proteins. Therefore, if the process of breaking down tyrosine is not functional it will result to build up of tyrosine and it’s by-products within body organs and tissues. Accumulation of this compound in the body will cause serious health problems.

Tyrosinemia disorder is categorized into three types which can be distinguished by their genetic cause and symptoms. These three types include; tyrosinemia type 1, tyrosinemia type 2, and tyrosinemia type 3. This research paper is mainly designed to deal with tyrosinemia type 1, its overview, current research, diagnosis, treatment and the current policy of the disorder.

Tyrosinemia Type 1

Firstly, let’s provide the synonyms of tyrosinemia type 17. This includes; hepatorenal tyrosinemia, fumarylacetoacetate deficiency, fumarylacetoacetate hydrolase deficiency, FAH deficiency, and hereditary tyrosinemia type 1. Tyrosinemia type 1, is the most relentless type of this disorder, this is because its signs and symptoms emerge at the first few months of infant life. When an infant is affected by the disorder he or she fails to add weight, and the patient will grow and develop at an abnormal rate.

Growth is affected by resilience due to the accumulation of protein food causing a high level of diarrhea and vomiting. In addition to this, infants will have the following signs and symptoms, yellowing of the skin, eyes turn to white, and a high susceptibility of nose bleeding. Severe levels of the disorder can lead to kidney and liver failure, weakening and softening of bones, also it increases the risk to be attacked by liver cancer. Untreated children may not survive beyond ten years1.

Above is the structure of tyrosinemia type 1. This disorder is usually inherited as an autosomal recessive pattern. According to biochemical and molecular research conducted on a two-month-old Hong Kong Chinese patient for tyrosinemia, the patient suffered from a final stage of liver failure, hepatic encephalopathy, and hypoglycemia.

The results from the doctors showed that there was an intense accumulation of multiple plasma amino acids, which included tyrosine, methionine, and phenylalanine, as well as N-acetyl tyrosine which causes liver failure as a result of tyrosinemia type 1 and non-metabolic conditions. This disorder affects 1 in 1000 individuals. Enzyme breakdown in the kidney involves a five-step process resulting in molecules that are used to produce energy and make substances in the body or excreted by the kidneys15.

Also, the FAH gene provides instructions for the fumarylacetoacetate hydrolase enzyme, which is useful in the final stage of tyrosine breakdown. Certain gene mutation such as FAH, TAT, or HPD causes a decrease in the enzyme breakdown of tyrosine. One of the most serious complications of tyrosinemia type 1 is the development of hepatocellular carcinoma, which occurs in older children.

Ultrasounds and alpha-fetoproteins are necessary for monitoring the serial liver. The observed biochemical abnormalities include exalted urinary levels of succinylacetone and hydroxyphenylacetic acids. Affected children have an increased concentration of tyrosine and methionine in the plasma, this leads to reduced activity of dioxygenase and methionine adenosyltransferase activity21.

Effects tyrosinemia type 1 on Organisms

Tyrosinemia type 1 has some adverse effect on other organisms which include pain in arms and legs, weakening of muscles, increased blood pressure and increased heart rate. People suffering from this disorder are highly susceptible to experience hallucination and seizures. In addition to this, galactosemia is a rare inherited disorder resulting from carbohydrates metabolism which affects the body ability to convert galactose to glucose. Ideally, galactose is converted by a series of three enzyme reactions to form glucose14.

At birth it is difficult to notice the signs and symptoms of either this disorder or galactosemia, this is because the signs appear after a few weeks, whereby the affected children lose their appetites and start vomiting excessively. Also, the disorder is accompanied by whites of the eyes and yellowing of the skin, enlargement of the liver, failure to add weight and abnormal growth. On adverse attack there could be an accumulation of fluids in the abdominal cavity and edema may occur10.

In conjunction with this5, the disorder involves transportation which is carried by the canalicular membrane. This membrane acts as a transporter of chemotherapeutic agents which are made of heterodimeric that transport sterols. There is a difference in the functioning between the base lateral membrane and the apical membrane.

These differences are as a result of some transporters facilitates the uptake of organic anions in exchange for bicarbonate or glutathione. In relation to this, the superfamily of solute carriers, have wide and peripherally overlapping substrate specificity. Exceptionally it transports the bile acids and its sodium bile acid only. Solute carriers are attached to the basolateral membrane by the trans-Golgi3.

Tyrosinemia Type 1

Current Research on Tyrosinemia Type 1

Tyrosinemia type 123 is a severe disorder which leads to great demise infant children; as a result of the fatality, it has lead researchers and medical professional to come up with recent studies on the disorder. According to 2 tyrosinemia type 1 is a disorder caused by a recessive autosomal; if the disorder is not treated it causes deaths to children.

In relation to5 on a screening of a newly born child, it is evident that when the process of screening is conducted with great accuracy and precision it is possible to identify the signs and symptoms of the disorder. The latest news on tyrosinemia indicates that it is a genetic disorder caused by elevated blood levels of the amino acid tyrosine, which is a building block for most proteins. Therefore, the malfunction of the multistep process that breaks down tyrosine will lead to accumulation of the product leading to serious medical problems which affect both body tissues and organs18.

According to researchers16 from Massachusetts Institute of Technology, they have developed nanoparticles that could carry CRISPR genetic editing systems deep within the cells and perform their normal operation on the DNA. This new technological development has lead to modifying the viruses on patients of this disorder. In this study led by Koch Institute Research Scientist Hao Yin and colleagues, they used this nanoparticle to remove specific genes in almost 80 percent of the liver cells test on mice.

This was the first successful experiment conducted by experts. The experiment utilizes tandem mass spectrometry to measure the amount of succinylacetone that is present in dried blood spots. The method has facilitated earlier detection of people who have and those who don’t have the disorder at a hundred percent rating3.

The most recent treatment strategy of tyrosinemia type 114 consists of a protein-restricted diet with medication of nitisinone. Nitisinone has led to great improvements in mortality and morbidity. According to17, acute management of liver failure can be treated through respiratory support, correction of bleeding diathesis, and appropriate body fluid management.

Chemically, nitisinone is made of para hydroxyphenyl pyruvic acid deoxygenated block; it is the second step in the degradation pathway which prevents the accumulation of FAA and its conversion to succinylacetone. The research also asserts that nitisinone should be treated and prescribed immediately after the diagnosis of tyrosinemia type 11.

Nitisinone increases the blood concentration of tyrosine; therefore, it is advisable to use diet low in tyrosine to prevent tyrosine crystals from forming in the cornea. This eventually leads to whites of the eye. In conjunction with this, dietary management should be taken into consideration whereby phenylalanine and tyrosine intake should be controlled using a vegetarian diet with low protein food and a medical formula. Initially22, liver transplantation was the solution to the disorder by eventually due to conducted research; liver transplant should only be done to patients with severe liver failure20.


Tyrosinemia type 1 diagnosis is conducted after clinical evaluation which involves going through the details of a patient history, and a specialized test conducted by experts. Sometimes17 the diagnosis of tyrosinemia type 1 can be suspended in instances whereby the infant displayed a failure to thrive or with an enlarged liver during the three months of life.

The diagnosis is possible when the tyrosinemia type 1 is detected in infants who have tyrosine metabolites and succinylacetone in their urine. In addition to this, diagnosis is possible during decreased activity of FAH in liver tissues. Doctors use molecular genetic testing for the FAH gene to confirm the diagnosis8.

The establishment of newborn screening programs can also be used to diagnose tyrosinemia type 1. Newborn screening involves measuring the succinylacetone to detect blood spots by tandem mass spectroscopy. Early screening of the disorder is very significant because it guides in the detection of tyrosinemia type 1, this can lead to treatment of the disorder to prevent its development to severe levels.

This practice is highly practiced all over the United States. Recent research has made it possible to carry carrier testing and prenatal diagnosis, this is possible by DNA analysis of the specific gene causing mutation in the family. Prenatal diagnosis also can result in the detection of succinylacetone in amniotic fluids11.


Currently, there is no cure for tyrosinemia type 16. However, individuals diagnosed with the condition should be subjected to a special diet restricted in two amino acids, which include amino acids and phenylalanine the entire life. Research also shows that patients affected by the disorder can be subjected to a treatment with a medication nitisinone. Caution the disorder should be treated as soon as possible after the condition has been diagnosed.

This medication (nitisinone) has been approved by food and drugs administration as a product for orphans diagnosed with this condition. In conjunction with this, treatment can also be facilitated by finding a medical specialist who is experienced in this disease. You can also visit a university or any other technical medical center which are more likely to the recent developments of the disorder technology and treatment30.

Recently studies conducted in the United States1 asserts that nitisinone should only be prescribed by a physician experienced in the treatment tyrosinemia type 1 since the accurate dose must be prescribed to each patient in relation to the specific biochemical test. Also, it is advisable to find a nutritionist skilled in managing this disorder. Blood tests should be conducted regularly to ensure consistency in the prescription of the right dose for patients.

With the aid of statistical information, this disorder affects infants at the ratio of 1is to 100000 in most areas but it is highly evidenced in Quebec, Canada. According to18 statistical information on prognosis shows that nitisinone treatment combined with a diet of low protein allows patients to thrive in good health. However, the prognosis is dominated by the HCC risk29.

Tyrosinemia Type 1

Current policies on tyrosinemia type 1

The concept-oriented clinical terminology has been developed by the United States standard for electronic health information exchange, whose great emphasis is on newborn coding screening and the use of terminology guide codes. Policies have been developed to ensure screening of newborn patients to diagnose the presence of tyrosinemia by observing the levels of tyrosine and phenylalanine.

Thus the following recommendations were made, if plasma concentration is raised, a high energy diet with a phenylalanine and tyrosine free should be supplemented. Also, natural protein should be given to the patients early once tyrosine concentration is falling. After treatment, all patients should be followed and analyze their development due to long-term risk complications. The use of nitisinone medication should continue without disruption. Failure to continuous medication can lead to serious complications such as acute liver failure, and a neurological crisis25.

In conclusion, tyrosinemia disorder is a genetic disorder characterized by increased levels of amino acid tyrosine in the blood. This disorder usually affects infants, whereby if untreated it can lead to adverse effects such as liver and kidney failure, weakening of bones, problems in the central nervous system and greater risk ok of liver cancer.

The condition is treated through diet management with low tyrosine and phenylalanine, soon after the disorder has been diagnosed with medication of nitisinone is used which prevents the second step in the tyrosine degradation. Newborn screening is the main process used to detect the presence of tyrosinemia type 1.


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Tyrosinemia Type 1

Sample Biology Prompt Structure and Function of these Four Macromolecules

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