Hello friends, today we will discuss about an important inborn error of metabolism that is alicaptonuria. It is an inborn error of metabolism of amino acid phenylalanine and tyrosine. Inborn error of metabolism of phenylalanine and tyrosine.
All of you know the pathway of phenylalanine that is phenylalanine is converted into tyrosine. Tyrosine is converted into para-hydroxy-phenylpyruvate which is converted into homogenity set. This homogenity set is converted into 4-mallyl acetoacetate.
This 4-mallyl acetoacetate is converted into 4-fumaryl acetoacetate, which is converted into pure marate. and acetoacetate. Tumerate will give you glucose.
Acetoacetate. And acetoacetate will give you fat. That's why these amino acids. Phenylalanine and tyrosine. They are known as both glucogenic and ketogenic amino acids.
Because they give glucose. And they give fat. So this is a. Outline of phenylalanine and tyrosine metabolism. In which it is converted into glucose and fat.
Now. There are some disorders. Due to deficiency of phenylalanine hydroxylase. Roxylase it is finished. phenylketonuria then tyrosine transaminase tyrosinemia type 2 then this para hydroxy phenyl pyruvate hydroxylase it is neonatal tyrosinemia Then homogentisate oxidase, this is the block in alkyl-captor urea.
Homogentisate oxidase leads to the alkyl-captor urea. So we will discuss this disease today. This is a block.
Okay, and this 4-mallyl-acetoacetate isomerase and fumaril-acetoacetate hydrolase, the deficiency of these two enzymes leads to the tyrosinemia type 1. Okay, this is an outline of phenylalanine and tyrosine metabolism. Conversion of phenylalanine. Phenylalanine to tyrosine by phenylalanine hydroxylase which leads to the disorder phenylketone urea.
Tyrosine transaminase deficiency lead to the tyrosinemia type 2. Parahydroxyphenylpyruvate hydroxylase deficiency leads to the disorder phenylketone urea. disease neonatal tyrosinemia and homogenetic oxidase deficiency leads to the alkyptonuria and formalyl acetate acetoacetate isomerase and formalyl fumaryl acetate acetoacetate hydrolyse lead to the disorder known as tyrosinema type 1. Now coming back to alkyptonuria it is a autosomal recessive disorder and the prevalence of the disease is one in 2,50,000 birds. This disease is typically characterized by deposition of alkylactone or alkylactone bodies. In the ear pinna, nose cartilage and intervertebral disc. They also get deposited in connective tissue of the joints that results in arthritis.
There is excretion of homogenicid. This homogenicid gets excreted in urine. Which on standing is converted into dark color.
So urine turns dark or urine turns black on standing when it becomes alkaline. It is a typical characteristic feature of Alkyl-Aptone urea. Now how Alkyl-Aptone is formed? Now this homogentisate is oxidized by oxidase into benzoquinone acetate. which on polymerization, which on polymerization, it gives alkyptone and this alkyptone get deposited in ear, nose, intervertebral disc, Disc Connective tissue of joints And the resulting condition is known as uchronosis.
It is known as uchronosis. Deposition of Alkapton in the ear, nose, intervertebral disc. connective tissue of the joint is known as a chronosis this is the pigment which get deposited and this is the condition who chronosis the disease is known as alkyl tone urea it is a inborn error of metabolism or to some other recessive disorder 1 in 2,50,000 live births, deposition of Alkapton in ear, nose and intervertebral disc and connective tissue of the joints. Deposition in connective tissue of the joints leads to the arthritis. So these are the symptoms of Alkaptonuria.
Laboratory diagnosis Laboratory diagnosis of Archaeopteryx urea, it is by, first by observation of urine, so urine, dark urine on standing or when it becomes alkaline, dark urine. on standing. It is a typical characteristic feature. Second, ferric chloride test is positive Empowered. Benedict test.
Benedict test. It is strongly positive due to the excretion of homogenity. In the treatment.
No specific treatment is required. This disease is not fatal. It is asymptomatic in most of the cases. When the person reaches to third or fourth decade of life.
this pigment got deposited in various tissues and causes the symptoms. So main treatment of the disease it is symptomatic treatment along with limit phenylalanine in diet. Alanine in diet less than 500 milligram per day. Limit phenylalanine in diet and symptomatic treatment.
So treatment generally it is not required because this is a benign condition. it is not fatal it is asymptomatic in most of the cases that's why treatment is not required the only treatment is limit phenylalanine in the diet summarizing the alkyptone urea it is inborn error of phenylalanine and tyrosine metabolism due to the defect in the enzyme homogentisate oxidase due to which homogentisate get accumulated homogentisate get converted into benzogynone acetate which on polymerization give alkyptone which gets deposited in ear, nose and intervertebral. disc and connective tissue of the joints resulting in condition known as uchronosis.
Then laboratory diagnosis by the typical characteristic of urine which turns dark on standing. ferric chloride test is positive and beryndic test is strongly positive. Treatment is not required.
It is asymptomatic and in the third or fourth decade of life when the alkyl ketone get deposited in the joints the treatment is required and limit the phenylalanine in the diet to less than 500 mg per day. We will discuss one case here. A 9 year old child brought to the hospital with complaints of black discoloration of ear and nose.
His urine turns black on standing and urine examination showed increased level of homogenetic acid. What is your opinion? probable diagnosis.
The diagnosis in this case is Alkyl Aptone urea. Then outline the biochemical pathway and name the metabolic defect that causes this disease. So outline the metabolic pathway the pathway and this is the defect in homogenetic oxidase which causes alkyptone urea leads to the formation of homogenetic which is diverted for alkyptone synthesis then state the changes in urine on standing in such patient changes in urine means the homogenetic get accumulated which is oxidized and turns into dark color What is the possible treatment? No specific treatment is required.
Limit the phenylalanine in diet. Then another question. give the at least two characteristic symptoms of the disease.
So urine turns dark on standing, arthritis due to alkylaptone deposition in joint, black deposits in ear and nose. So this is all about alkylaptoneuria. Keep watching.
Thank you.