A&K connection signing off

Hey guys, it's the A&K connection!

Hopefully you guys have been missing us, because we sure miss you!

We received really great feedback from all of you throughout our entire blog so far. In particular, one of our most popular and well liked post was on the History of Alkaptonuria. Many of you loved the video and we are more than appreciative of all the support.

But we cannot truly express our appreciation by simply saying thank you...

So for the first time ever, just for you special folks out there, we made a game.

Yes, we made a game for YOU. Because we love you.

Now, it is a very simple text game, kind of like a role playing game, but the game is all about alkaptonuria, just like our blog :) You get to make choices which affect how the game reacts to your answers.

To play it, you'll have to download it from Dropbox. Just follow the link. Once it's downloaded, just click it to play!

https://www.dropbox.com/s/kb074i8e6m466dz/Alkaptonuria%20quiz%20game.exe?dl=0

Disclaimer: Your computer will tell you the file is infected with a virus. Rest assured, the file is safe. It automatically labels it as unsafe because the publisher (me) is unknown. Scan it with your antivirus software and you will see that it is perfectly safe.

And with that, time to say goodbye...

Stay classy Broritos.

A&K connection

signing off

Treatment

Treatment

Hello broritos

Today I am going to talk about the available treatment for Alkaptonuria.

Unfortunately, there is no available cure for Alkaptonuria. However, there are treatments for symptom relief and prevention of further complication. According to a doctor in Liverpool, cure for Alkaptonuria is possible in the next 10-15 years using gene therapy.

Finally, some good news for Alkaptonuria patients.

WELL !! THERE IS NO CURE!! BUT, AT LEAST THERE IS TREATMENT :)

1)Nitisinone is a drug administered to reduce HGA level. Currently, Nitisinone is in advanced clinical trials.

Nitisinone inhibits the enzyme 4-hydroxyphenylpyruvate dioxygenase which is required to convert 4-hydroxyphenylpyruvate to HGA.Thus by taking in nitisinone, the body’s HGA drops as HGA is not produced anymore. In some research studies, the amount of HGA released in the urine dropped by 95%. However, significant improvement in mobility and musculoskeletal function was not observed. In most patients, side effects were not observed although a handful had side effects such as corneal crystals, liver transaminase and elevated plasma tyrosine level (tyrosinemia). Most of these side effects were noticed during short trials such as 15 weeks.  Long time side effects are still unknown. Furthermore, a patient under nitisinone is theoretically able to develop neurologic complications associated with tyrosinemia type III. Another effect of high plasma tyrosine levels is irritation in the corneas.

Yea, you may not want those contacts buddy...

But you may be wondering, aren't those side effects really bad? Tyrosinemia is no joke! And you're absolutely right. But research has shown that very simply it can be alleviated by restricting on foods with high tyrosine and phenylalanine content, such as cheese, nuts, milks and some meats.


Homer thinks this should be in the Complications section of Alkaptonuria

2) Low protein diet has shown to reduce the amount of HGA in the urine. However, long term side effects are possible and it is not a practical for daily living

MORE WEIGHTS, MORE PROTEIN!! WHO CARES ABOUT ALKAPTONURIA!! 

3) Increasing vitamin C uptake has been hypothesized to prevent deposition of ochronotic pigments on the bones and slow down arthritis. However, the amount of HGA excreted in the urine remains the same and consuming way too much vitamin C might possibly contribute to elevated HGA levels as it increases tyrosine synthesis.

4) physical activity such as swimming will help alkaptonuria patients to maintain bone and muscle strength. However, high impact sports such as weight lifting should be avoided as it can further damage the bones.


WHY IS THERE NO FISH IN THIS POND !!!!

OK GUYS !! HOPE U GUYS ENJOYED OUR BLOG!! HAVE A GREAT YEAR AHEAD!!

PEACEOUT
A&K CONNECTIONS

Diagnosis

Diagnosis/testing

Bonjour Broritos !!! Hope u guys are having a wonderful start to 2015

Usually Alkaptonuria is either detected at a very early stage of life or during adulthood. Alkaptonuria is detected at a very early age when the oxidised form of HGA,Benzoquinone acid( turns urine to black ) is found in diapers. During adulthood, alkaptonuria patients gets diagnosed when they complain of back and joint pain.

Confirmation of alkaptonuria is through gas chromatography-mass spectrometry analysis. A patient with alkaptonuria will have about 1-8 g of HGA in the urine.

You might be wondering what is gas chromatography-mass spectrometry. It is the combination of both gas chromatography and mass spectrometry. In gas chromatography, the molecules are separated based on interaction with stationary phase(column). Molecules with stronger and frequent  interaction with stationary phase will elute out later. The mass spectrometry is located downstream to break each molecules to ionized fragments and detect these fragments using charged to mass ratio.

Other diagnosis include urinalysis. In this method, ferric chloride is added to see whether the urine turns black in colour.

Furthermore, it is also commonly associated to symptoms such as moderate pain during urination and frequent fainting after urination during the night. In case you guys didn't know, the black urine actually looks normal when its freshly passed, it only turns black after a while because it is oxidised by the air. And interestingly, alkali speeds up that oxidation process. That means doctors can use substances like caustic soda or caustic potash to make the urine sample alkaline, which is then placed on sensitised photographic paper, turning the paper black (positive test). So diagnosis this way, is really easy and fast! 

NO GRANDPA! Just because your pee's black doesn't mean it's gasoline!!!

Testing

Molecular genetic testing is also available to measure the risk of a family member inheriting the disease.

OOOOOOOOOOOOhhhhhhhhhhhhhh Noooooooooooooooooooooooooooooo!!!!!!!!!

I am tested positive for Alkaptonuria:(

Next up :Treatment

PEACE OUT

A&K CONNECTIONS

pathophysiology

Pathophysiology

WAZZZZZZUP Broritos,

TODAY we are going to talk about pathophysiology

The homogentisate 1,2-dioxygenase(HGD) requires 6 subunits to form 2 HGD trimer which in turn forms a bioactive HGD hexamer. The HGD uses Fe2+ and O2 to cleave the aromatic ring of the homogentisic acid(HGA)to form maleylacetoacetic acid.However, a mutation in one or more of the 6 subunits will interfere with the formation of the HGD trimer.Thus, there will not be any bioactive homogentisate 1,2-dioxygenase.

That is all for today !!! Hope abit of pathophysiology was interesting

Peace out

A&K connections

Genetics

Genetics

Hey broritos, Hope u guys had a great Christmas

Today, we are going to talk about genetics. Fret not cuz today’s genetics part will be very straight forward and interesting at the same time.

Now I am going to talk about the location of a gene or in other words locus

Firstly we must learn how to read cytogenetic location of a gene!! So here is a diagram to help u guys with it :)

Cytogenetic location:7q31.2.

We are using CFTR(Cystic fibrosis transmembrane conductance regulator) as an example.The first number 7 indicates the chromosome number. In humans we have 23 pairs of chromosome. So, in this case the CFTR gene is located on the 7th chromosome.

The q represents the arm of the chromosome. Every chromosome has two arms which are p and q. The p represents the short arm and q represents the long arm. Both arms are “divided” by a centromere.Hopefully, the diagram below shows a better illustration.

Next, the number 3 represents the region and 1 represents the band. These region and bands are obtained when the chromosome is stained in a certain way.Then, the bands are visualized under microscope.(region and band number count starts from centromere and ends at the telomere)  After the region and band number, there will be a number after a decimal point, this number indicates the subband which can be visualized under microscope with higher resolution within the normal bands.

Hopefully the above explanation gives a clearer idea on gene location

SO Where is HGD gene found??

Cytogenetic location : 3q13.33

Other than the cytogenetic location, there is also the molecular location which use base pairs to locate the gene.  For the HGD gene, the gene is located base pairs 120,628,167 to 120,682,570 on chromosome 3

Hope the gene location was educational. Now, we are going to talk about autosomal recessive

Remember us saying that the gene is transferred to the affected individual in an autosomal recessive manner!!

Autosomal refers to a mutation in one of the first 22 non-sex chromosome.

So what is recessive?

Genes come in pairs. Therefore, Recessive means that both genes must be defective for the disease to occur.

Lets use this diagram to help us understand recessive

X-dominant gene

x- recessive gene.

XX- unaffected by disease and not a carrier

Xx-unaffected by disease and is a carrier

xx- affected by disease

Only a child with xx be affected with disease.Thus, if both parents are carriers to a defective gene, the child will be 25% likely to inherit the disease, 50% likely to be carriers and 25% likely not to carry the mutant gene.

SOOO , A person must be very unfortunate to inherit an autosomal recessive disease. More so , if it is a rare disease like Alkaptonuria.

WHY ALWAYS ME ??

Currently over 100 mutation of HGD gene has been identified

That's all from us today

Next blog: Pathophysiology

PEACE-OUT

A&K connections

History of alkaptonuria

Welcome back Broritos to a very special blog from your own A&K connection!

Oh but before I forget…

Merry Christmas Eve! XD Yayyyy!!!

Today’s blog is a little less on the hard science and more the fun part of it! In fact, we are going to take u guys through a very short history “lesson” on Alkaptonuria. Don’t worry guys, this’ll be a lot more fun than history lessons in secondary school!

 

Why you ask? Well that’s because we made you Broritos a special video on the history of Alkaptonuria as your Christmas present! Enjoy and don’t forget your delicious snacks! :D

Of course for those of you who are interested to know more in detail, I’ve written it down below for you guys:

Alkaptonuria was first discovered by a british physician named Sir Archibald Garrod (1857-1936) in 1901. He showed great interest in his patient’s urine and one day, examined a three-month-old patient called Thomas P. He saw an unusual bluish black stain on the diaper (remember that during those times Alkaptonuria was an unknown disease). Later, Thomas’ two other siblings were born and also had the same black diaper stains. Thomas’s parents were actually cousins (unaffected from disease) and their mothers were siblings. One day, Sir Garrod read bateson’s description on Mendel’s work and soon everything becomes much clearer. He discovered that Thomas’s parents each contributed a mutated allele causing thomas and his siblings to inherit the disease.He credits Mendel’s law for his sudden realization. SIr Garrod was the first pioneer to link hereditary to metabolic linked diseases. He called such diseases “inborn errors of metabolism”. Just like many other great scientists,Sir Garrod’s work was not recognised and appreciated during  his lifetime. SOOOO SAD:(

(Fun fact: Sir Garrod’s father was the first person to discover abnormal uric acid metabolism and his daughter was the first women to hold an oxbridge chair

(Another fun fact: An egyptian mummy named Harwa suffered from Alkaptonuria during 1500 BC)

ALRIGHT BRORITOS!! Hope u had a fun history lesson

PEACE OUT

complications from Alkaptonuria

Hola broritos,

Hope you guys enjoyed our last blog :) Today we are going to learn something new and more interesting

In my previous post I mentioned that Homogentisic acid(HGA) is toxic to the body and causes three major complications.

So now, lets talk about how HGA causes the three major complications

Lets go bros!!!

The first complication is black urine, and if you’ve been reading our blog, you’ll know it’s because of HGA in the urine. HGA gets readily oxidised when exposed to oxygen from air causing it form a new compound called Benzoquinone acetic acid (BQA). The substance BQA causes the urine to appear black. However, the actual darkening of urine will only occur after several hours and many individuals never observe any change in colour of urine! They are  unaware of their genetic disease until other complications start to appear. How scary is that?!           ````````````````````````````````````````````````````````````````````````````````````````````````````````````````````

Ew! Imagine how terrifying that would be if you saw that in your toilet!

But enough scary thoughts of black urine, look at how cute this little fella is! Awwww :3 Shout out to the awesome Adventure Time!

The second complication is Ochronosis (Bluish black pigmentation of connective tissue). Ochronosis occurs after the age of 30.This is when most individuals will start to recognize that they inherit Alkaptonuria. Brown pigment is observed at the sclera of the eyes. Brown pigment deposition can also happen in the conjunctiva and cornea. Fortunately, the brown pigments will not have any negative impact on the vision. Another organ with pigmentation is the ear helix. A bluish gray pigment can be found at the ear helix.At the same time, the ears may start to calcify. Purple or dark discolouration forms on the hands of the affected patients and pigments can be released through sweat which can stain the clothes.

I’d hate to imagine what his sweaty clothes would be like if he had Alkaptonuria! Yuck! Dx

The third complication is Osteoarthritis. Arthritis is a form of joint disorder that involves inflammation of one or more joints. This complication rises when an affected individual reaches 30-40 years old. Osteoarthritis occur when BQA binds to the bond causing them to be black and brittle. Osteoarthritis begins in the spine, causing the spine to narrow and forcing the it to go through ankylosis spondylitis ( vertebrate of spine fusing together). This limits the spine’s flexion. Afterwards, the osteoarthritis spreads to other part of the body such as knees, shoulders and hips. The bones start to degrade and break into tiny fragments. This is a very painful process and patients usually complain of their bones grinding against one another.
 

“Granny, no! Your arthritis!” *snap* D:

Here’s a fan service to all you Cat lovers ;3

But unfortunately, these are the ONLY the three common complications arising from Alkaptonuria. (So horrible to think there’s more! D:) Other possible complications include heart, kidney and prostate (OUCH!) problems. HGA gets deposited on the valves of the heart causing them to be brittle and black as well.Moreover, it can also weaken and stiffen the blood vessels which increases the risk of heart diseases. This usually affect patients of 60 years of age and above. It can also lead to renal and prostate stones.

For any of you Lord of the Rings fans. I know I am ;)

Thank you, Hope u broritos enjoyed our blog

Peaceout

A&K connection