Alkaptonuria Autosomal Recessive Disease Biology Essay

Alkaptonuria, besides known as black urine disease, is a rare autosomal recessive upset which occurs due to a mutant in the HGD cistron. The HGD cistron provides instructions for doing an enzyme called homogentisic acid oxidase ( HGAO ) , which is the enzyme that helps in the dislocation of the amino acids tyrosine and phenylalanine. Tyrosine is a non-essential amino acid with a polar side group and it has a particular function by virtuousness of the phenol functionality.

It occurs in proteins that are portion of signal transduction procedures. On the other manus, phenylalanine is an indispensable amino acid classified as non-polar because of the hydrophobic nature of the benzyl side concatenation. It is a precursor of tyrosine, and besides a direct precursor to the neuromodulator phenylethylamine, normally used as dietetic addendum.In patients with Alkaptonuria, there is lack of the enzyme homogentisic acid oxidase ( HGAO ) , as a consequence, homogentisic acid, which is produced in the improper dislocation of tyrosine and phenylalanine accumulate in the organic structure.

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Excess homogentisic acid accumulates in the blood and besides in the connective tissues particularly around articulations. This leads to development of ochronosis, arthritis and many more complications seen in patients with Alkaptonuria. Therefore, Alkaptonuria is fundamentally a upset which consequences due to improper dislocation of tyrosine and phenylalanine owing to the lack of the enzyme HGAO.

Excess Homogentisic acid in blood leads to its elimination in the piss, and this makes the urine bend blue-black ( dark ) when exposed to air. A high urinary degree of homogentisic acid is defined as greater than 4-8 gms in a 24 hr period. In kids, dark staining of the nappies sometimes can bespeak Alkaptonuria.

It is of import to observe that most patients are non cognizant that they have the disease until they are about 30 to 40 old ages of age. There is inclination of males to hold earlier oncoming of creaky symptoms with higher badness than females, although the ground for this difference is ill-defined but to me, it may be because males do more of mechanical work than females, which might be a ground for them to hold more terrible creaky symptoms.Alkaptonuria, although has no presently known remedy is non life threatening, possibly because it does non impact badly most of the critical variety meats in the organic structure. That is to state that, if the upset is known by any agencies to impact organ like the liver or the encephalon every bit good as other critical internal organ it may take to many more complications like mental deceleration or interfere with other metabolic procedures which may or can take to early decease.Typically, patients with Alkaptonuria require womb-to-tomb intervention to help the direction of the symptoms and complications of this upset, but they are expected to populate comparatively normal and healthy lives.

Alkaptonuria, being an inherited upset, has a hazard factor of household history. It is known that it affects work forces and adult females in equal Numberss. The prevalence is estimated to be approximately 1 in 250,000 people worldwide. Newborn testing for this upset is NOT widely practiced, which may be because the upset is non life endangering and can be managed really good for patients to populate a normal life.

But the consequence of this has made it hard to gauge the figure of instances of Alkaptonuria. It is known that some people may hold the mutant that causes this upset but do non demo the symptoms.SuggestionI believe every upset can be treated or managed decently if it is detected and disgnosed early.

Example is in the instance of malignant neoplastic disease. Cancer may get down as benign tumour which grow from a individual malignant neoplastic disease cell. If detected and diagnosed early, it can be eradicated in a well fashioned manner without any complication. But if it is diagnosed or detected tardily, when the malignant neoplastic disease cells has spread through lymph nodes and blood vass to other tissues, it can ensue to other serious complications and can take to decease. In order to avoid the complications of Alkaptonuria like arthritis, brickle bosom valves etc, the newborn showing for this upset will make a batch of good and benefit to people with this upset because early diagnosing of the upset can assist cut down serious complications of the disease in ulterior old ages.Hazard Factors:AUTOSOMAL RECESSIVE INHERITANCE:As said earlier, Alkaptonuria is an autosomal recessionary upset. This means that an single must inherit two mutated allelomorphs of the disease-causing cistron one from the male parent and one from the female parent in order to hold the disease.

Carriers of this disease are single who possess merely one mutated allelomorph of the disease-causing cistron and they do non demo or see the symptoms but they may go through the mutated cistron to their progenies.If merely one parent is a bearer, there is a 50 % opportunity with each birth that the kid will go a bearer but 0 % opportunity of really inheriting the disease.If both parents are bearers, there is a 25 % opportunity with each birth that the kid will inherit the disease, a 50 % opportunity that the kid will be a bearer, and a 25 % opportunity that each kid will non inherit either mutated allelomorph.If both parents have the disease, there is 100 % opportunity that their progeny will hold the disease.EthnicityThe frequence of Alkaptonuria is higher in certain population. In certain countries of Slovakia, Alkaptonuria affects about 1 in 19,000 people. It has been noted to be common besides in the Dominican democracy in which the prevalence is non known.

Ethnicity is known to play some variable functions in certain diseases, merely like the instance of reaping hook cell anaemia which affects more of the African American population than the white population.General: Because Alkaptonuria is inherited in an autosomal recessionary manner, theonly hazard factor is a household history of the upset. Men and adult females are affected in equal Numberss, and the prevalence is known to be 1 in 250,000 people worldwide. It is hard to gauge the figure of instances of Alkaptonuria because newborn testing for this upset is non widely practiced and some people that have the mutant that causes the upset do non demo the symptoms.Cause:Alkaptonuria is caused by a defect, or mutant in the HGD cistron which provides information for doing an enzyme known as homogentisic acid oxidase ( HGAO ) as mentioned earlier. More than 80 different mutants associated with Alkaptonuria have been identified in the HGD cistron.

The normal map of the enzyme HGAO is to assist in the dislocation of the amino acids phenylalanine and tyrosine. Lack of this enzyme will ensue in the accretion of homogentisic acid which is produced in the improper dislocation of phenylalanine and tyrosine. Excess homogentisc acid in the blood and besides in the connective tissue lead to ochronosis, bluish black urine etc.

Besides as an familial upset, the cistrons are inherited on allelomorphs or familial discrepancies of a specific cistron.SIGNS AND SYMPTOMS:BLACK URINE: Urine from patients with Alkaptonuria turn blue-black when exposed to air. This is because of the buildup of homogentisic acid in the piss.Heart: The aortal and mitral valves, which control blood flow to the organic structure are most affected by the accretion of homogentisic acid which causes calcification of the valves around age 60. Deposits of homogentisic acid can take to the formation of atherosclerotic plaque, which can take to coronary arteria disease. This complication may ensue to decease if non decently treated or managed as it is known that coronary artery disease id the taking cause of myocardial infarction which can ensue to decease if non decently treated.Joints: The buildup of homogentisic acid in the articulations particularly the spinal column, hips, shoulders and articulatio genuss is the cause of the creaky symptoms seen in patients with Alkaptonuria.

Pateints may besides develop degenerative arthritis, which is a degenerative articulation disease associated with painful articulations and arthropathy, or morbid articulations.Ochronosis: This is the physique up of dark pigments caused by the accretion of homogentisic acid in connective tissues such as gristle and tegument.Skin: Patients with Alkaptonuria have blue-black speckled stain of the tegument. This is most noticeable in countries where the organic structure is exposed to sun and where perspiration secretory organs are located. The ear and sclerotic coat of the oculus may look grey blue.

However, vision is non normally affected.OTHER: In work forces, the prostate is frequently affected. The sedimentations of homogentisic acid can organize rocks in the prostate and kidney.

Ear wax exposed to air turns black depending on the sum of tyrosine and phenylalanine in the diet after several hours. This is a typical feature of Alkaptonuria.DiagnosisGENERAL: Alkaptonuria can be diagnosed based on symptoms of skin colour, joint uncomfortablenesss and urine samples. The diagnosing can be confirmed by verifying household history of the disease, microscopic scrutiny of the tegument cells. In proving, a high urinary degree of homogentisic acid is defined as greater than 4-8 gms in a 24 hr period. It is necessary to observe that homogentisic acid is non usually excreted in the piss of healthy persons.Chromatography: Paper chromatography and thin bed chromatography can be used in the diagnostic testing performed on blood sample to observe high degrees of homogentisic acid.GENETIC Testing: Knowing the specific mutant that cause the upset within a peculiar household can assist in the trial of DNA of an person to look for the presence of the specific mutant.

This is done byblood sample analysis.BLACK URINE: Urine from patients with Alkaptonuria turn blue-black when exposed to airPrenatal Diagnosis: This type of proving is done by chorionic villus sampling, amniocentesis or blood collected from the umbilical cord.X-RAYS: X ray can assist place complications such as degenerative fussion of vertebrae.Complication:Arthritis: Alkaptonuria patients finally experiences declining arthritis particularly in the shoulder, hip and spinal columnBreathing: Accretion of homogentisic acid in the gristle of treachea, voice box and bronchi causes failing of these tissues. This may interfere with address and external respiration.

Heart: Failing of bosom valve and hazard of coronary bosom disease are seen as complications of Alkaptonuria.OTHER: The cardinal nervous system and the endocrinal variety meats may be affected. In work forces, the prostate is frequently affected taking to prostate rocks.Treatment:GENERAL: There is presently no known remedy for Alkaptonuria, but intervention can assist to cut down symptoms and for proper direction.Diets: Low protein diet particularly in the amino acids tyrosine and phenylalanine aid to cut down homogentisic acid, thereby cut downing the sum deposited in organic structure tissues.

Medicine: Patients with Arthritis may take non-steroidal anti-inflammatory drugs ( NSAIDs ) or Acetaminophen to alleviate hurting and redness. There has been research of limited usage of nitisinone, which is an inhibitor of homogentisic acerb oxidase ( HGAO ) which plays a function in the formation of homogentisic acid. Nitisinone shuts down the enzyme wholly forestalling formation of homogentisic acid. Eye annoyance may be a side consequence.Surgery: Older patients may necessitate surgery to rectify merger of vertebrae and joint replacing.

VITAMIN C ( ascorbic acid ) : Some patients benefit from high doses of vitamin degree Celsius which has been shown to cut down the buildup of homogentisic acid in the gristle of the ears, which may bespeak that there is less homogentisic acid in the remainder of the organic structure and may demo the patterned advance of arthritis.Prevention:There are presently no known method of forestalling this upset. Persons with familial sensitivity for this upset can take stairss to decelerate the disease patterned advance, such as by eating healthy nutrient free from proteins and besides by exerting on a regular basis. Peoples with household history of this disease should see the physician on regular bases.GENETIC Guidance: This will assist persons. Families and twosomes affected or at hazard of the disease to program and pull off the disease in a better manner.

PRENATAL Testing: Prenatal testing is necessary in order to cut down serious complication that may come up as a consequence of this upset in ulterior old ages. It can besides assist in proper direction of the disease if a newborn is known to inherit the disease.CASE STUDYA male baby of 7months old, boy of a non-consaguineous twosome, noted by the parents to hold blackening of his apparels and nappies moistened with piss when left unwashed for some hours. He has a 4 twelvemonth old sister with the same ailment, other of his siblings ( two brothers ) were normal. There was no medical job in the household. Growth and development of the senior instance was normal. Physical scrutiny revealed no abnormalcy.

There was no pigmentation of the sclerotic coat and the ear lobe gristle. Joint scrutiny was normal. The piss of both the instances appeared normal on aggregation but turned blue-black on drawn-out exposure to the ambiance. Everyday research lab probes were normal and radiological scrutiny showed no degenerative alterations in the articulations ( hip, shoulder and spinal column ) . The paper and thin bed chromatography revealed the presence of high sums of homogentisic acid in the piss. Both of them were prescribed ascorbic acid ( vitamin C ) 500mg BD and low protein diet. Currently both of them are symptomless.

Decision:This instance survey suggests an autosomal recessionary type of heritage already established in Alkaptonuria although there is no blood kinship. My suggestion earlier in this text comes into drama here as early sensing being really of import for the bar and intervention of multiple systems upsets and the complications of Alkaptonuria. The parents being able to observe the discolorations in nappies helped in the early diagnosing of this upset which helped in the proper direction and cut down the hazard of other complications. These kids being symptomless can populate a normal life without any complicated in linked to Alkaptonuria in subsequently old ages.


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