Living with Pompe disease

Hello guys :) This week we will deviate from the usual scientific jargon
of Pompe disease and explore something closer to real life. We have
previously talked about what caused Pompe disease and what are the
symptoms, but words are just words. We probably have not met someone who
has Pompe in our life (yet), so we would not have any idea how Pompe
patients live their lives and what impact the disease has brought to
them and their families. So today we shall have a quick look into the
lives of Pompe patients via a short video clip, enjoy :)

*Watch the video here!* http://youtu.be/Z_l99WiOE-o


Hope you have gained some insights on the life of Pompe patients and
their families. As you can see, Pompe has a great impact on the quality
of life as even the simplest tasks may be a challenge. The emotional
aspect is also an important area of concern as many people breakdown
when hearing that their loved ones are diagnosed with Pompe. However,
there are support groups available to provide support to Pompe patients
and to help them overcome the emotional burden.

Here is the link to one of the handouts given to Pompe patients to help them adapt to the disease, so do take a look :)

http://www.australianpompe.com/wp-content/uploads/2014/06/pc_08_en_2011_the_emotional_impact_of_pompe_disease1.pdf

So if we do come across someone with the disease we should try to
understand their situation and not judge, because now we have a better
understanding on what they are going through. So do show them your
support and concern! <3

If you have any comments
regarding the lives of Pompe patients or would like to express your
views, please do post them below!! Looking forward to seeing your
comments! :))

See you next time!

Mei Ying

Symptoms

Hi guys, I'm back!  In the previous post, we have discussed about the causes of Pompe disease. Today, I am going to be sharing with you guys on the symptoms of the disease.

So, how do you know if someone has Pompe disease? Well, the signs and symptoms of the disease actually varies from patient to patient. However, there are several general symptoms such as muscle weakness in arms and legs, muscles for breathing and the heart in infants.

For infants(infantile form) with Pompe disease, they have extreme muscle weakness and displays a "floppy" appearance. X-rays will usually show a greatly enlarged heart. Other common symptoms among infants include breathing difficulties, trouble feeding and failure to meet developmental milestones such as rolling over, and sitting up. This infantile form of the disease usually comes into medical attention within the first few months of life.

The usual symptoms that are displayed includes:

• cardiomegaly
• hypotonia
• cardiomyopathy
• respiratory distress
• muscle weakness
• feeding difficulties
• failure to develop (sitting, rolling) 
• floppy appearance 

Floppy appearance (http://www.pompesa.co.za/wmenu.php)





Certain facial features that are displayed also include macroglossia, whereby the patient's tongue is enlarged, mouth and eyes wide open and poor muscle tone.

For children and adults (the late onset form), they tend to display a greater variety of symptoms, including weakness of the leg and hip muscles, leading to mobility difficulties, and breathing difficulties. Older patients however, don't usually have the heart problems typical in infants. They have more prominent skeletal involvment, especially the lower limbs.

The more common features displayed includes:

• impaired cough
• recurrent chest infections
• hypotonia
• progressive muscle weakness
• delayed motor milestones
• difficulty in eating (swallowing & chewing)

So, this concludes the end of our post on the of symptoms Pompe disease. Feel free to ask any questions in the comments section (if you have any!)

Till next time!
Rose


References:
http://en.wikipedia.org/wiki/Glycogen_storage_disease_type_II#Signs_and_symptoms
http://www.pompe.com/patients/signs-symptoms.aspx

History of Pompe disease

Hi guys! Today, I am going to be sharing with you people about the history of Pompe disease. To begin, why is Pompe disease named Pompe disease? To clarify, this disease has nothing to do with the city Pompeii ( an ancient Roman city that was buried under volcano ashes after a volcano erupted).

The disease is actually named after Joannes Cassianus Pompe (1901 - 1945), a Dutch pathologist who characterized the disease in 1932. He described this disease as the accumulation of glycogen in muscle tissue in some cases of a previously unknown disorder.


Joannes Cassianus Pompe(http://pompestory.blogspot.sg/2009/04/joannes-cassianus-pompe-1901-1945.html)

 The basis of the disease remained a mystery until 1955, when Christian de Duve (1917-2013), a Nobel prize winning Belgian cytologist and biochemist.. Christian de Duve discovered lysosomes (which got him his Nobel prize), which led to his co-worker Henri G. Hers (1923-2008) to realise that the deficiency of a lysosomal enzyme for the breakdown of glycogen - alpha glucosidase, could explain the symptoms of Pompe disease.


Christian de Duve (http://www.nobelprize.org/nobel_prizes/medicine/laureates/1974/)

Despite recognizing the basis of the disease, it was difficult to find the appropriate treatment. Attempts to administer the enzyme led to its uptake by the liver instead of the target location - the muscle cells, where it is needed.

In the 1990s, two Dutch scientists, Arnold Reuser and Ans van der Ploeg a PhD student were able to show an increase in the enzyme's activity in the normal mouse muscles by using alpha glucosidase containing phosphorylated mannose residues purified from bovine tests.

In 1998, Dr Yuan-Tsong Chen and his colleagues at Duke university demonstrated for the first time that the enzyme alpha glucosidase (produced in Chinese Hamster Ovary cells), can actually clear the glycogen in the muscle tissue and improve the muscle function (in Pompe disease quail). This demonstration was later followed by the production of clinical grade alpha-glucosidase. This work eventually culminated in the start of clinical trials, with the first clinical trial including 4 babies receiving enzyme from rabbit milk and 3 babies receiving enzyme grown in Chinese Hamster Ovary cells.

 
Dr Yuan-Tsong Chen (http://www.aaezine.org/articles/vol23/23N2ExtraordinaryMeasures.shtml)

 SO, we've come to the end of our little history lesson. Hopefully you guys have learned something!

Rose

References: http://en.wikipedia.org/wiki/Glycogen_storage_disease_type_II


 
 
 

What causes Pompe Disease (additional info for those who wants some challenge)

Hey guys! Hope you had a good break from the previous post! ;)

For those of you who wants to learn more and want to take up some challenge, this section is for you! If you think that you have had enough and your brain can't absorb anymore info, you are free to skip this part! We are totally cool with it :)

Remember in the previous post I have mentioned that mutations causes the GAA gene to be defective? Well what exactly are these mutations? To date, there are more than 200 different type of mutations of the GAA gene recorded that causes Pompe. Some of these mutations are caused by substitution of amino acids while some are insertions or deletions. This can result in missense mutations which can totally change the function of the protein produced (in this case changes the function of acid alpha-glucosidase such that it does things that it wasn't originally supposed to do) or it can result in nonsense mutation where the polypeptide sequence is shorter than usual and it can't perform its function. As a result, the production of fully functioning acid alpha-glucosidase enzyme is greatly reduced, resulting in Pompe disease.

One common example of a substitution mutation in the GAA gene is the substitution of Glutamic acid for Aspartic acid at the codon 645. This mutation affects the post-translational modification of the acid alpha-glucosidase enzyme which results in the production of a non functional enzyme.

There are many many more such mutations that causes Pompe disease which makes it impossible to explain each and every one of it. However you've got the gist of it and I hope that this will encourage you to explore further ;)

(http://imindmaps.blogspot.sg/2013/10/mutations-in-dna.html)

~Mei Ying

References:
http://ghr.nlm.nih.gov/gene/GAA
http://www.pompe.com/healthcare-professionals/genetics-epidemiology/mutations.aspx
https://catalog.coriell.org/0/sections/Search/Sample_Detail.aspx?Ref=GM01935&product=CC

What causes Pompe Disease?

Hello guys, I am back!! :D

This week we will be a little more intensive and examine the science behind Pompe. Are you ready?! Of course you are! I can sense your enthusiasm!! XD Now lets get started shall we?

As mentioned in the previous post, Pompe patients are unable to break down glycogen in their cells unlike non-sufferers. But why is that so? Today I am going to answer your question.

First of all lets go to the root of the problem which is the genetics (remember I have mentioned before that the disease is genetic?). There is one gene in your genome called the GAA gene which codes for the acid alpha-glucosidase enzyme. This is the enzyme which breaks down the glycogen by hydrolysing α-1,4- and α-1,6-glucosidic linkages in glycogen (don't worry if you don't understand this part! It just basically means the enzyme breaks these 2 types of bonds which holds the glycogen molecule together!). However for people with Pompe disease, there is a mutation in the GAA gene which cause a defect in the enzyme production, so no or very little acid alpha-glucosidase is produced.

Both glycogen and acid alpha-glucosidase are found in little packages in muscle cells called lysosomes. The job of alpha-glucosidase is to break down the glycogen in the lysosomes so that the glycogen will take up less space in the lysosomes. But if acid-alpha glucosidase is not present, the amount of glycogen will keep increasing in the lysosomes until the lysosome swells beyond the normal size. This can disrupt cellular functions in the muscle cells and the lysosomes can even burst, damaging the cell and the surrounding tissues. Ouch :(


(http://www.pompe.com/patients/about/cause.aspx)
Here is a picture of what is going on inside a muscle cell of a person suffering from Pompe.
Myofibrils are structures found inside muscle cells that controls muscle contractions.

As you can see, glycogen can be found all over the muscle cell, interfering with the myofibrils and causing disruptions in the cell.  This causes the symptoms of Pompe which includes muscle weakness and breathing difficulties (as respiration is controlled by muscles too).

(http://blogs.lt.vt.edu/joneill/2012/09/17/extraordinary-measures/)

Since Pompe disease is genetic, it can be passed down from generations to generations. This disease is an autosomal recessive disease, meaning that you have to inherit the defective gene from BOTH parents to be affected. Or if only one of your parents carry the disease while your other parent is normal, you will be a carrier and you can pass down the defective gene to your children too. Sounds quite scary doesn't it :(

(http://www.pompe.com/patients/inheriting-pompe.aspx)

 Here is a chart showing how the inheritance of the disease works. Alleles basically means different forms of the same gene. In this case, there is the abnormal allele of the GAA gene which can cause Pompe disease and the normal allele of the GAA gene which won't cause Pompe disease.

*Do note that even though there are different type of Pompe disease (early-onset/late-onset), the basis behind the disease is the same.

Phew, that was lengthy wasn't it. The good news its that this is all we have for now! :D Time to give that brain of yours a break!

If you have any questions regarding what was mentioned in the posts (including this one) please feel free to comment below! We will try to answer your questions and maybe even discuss about it :)

See you next time!

~Mei Ying

References:
http://www.pompe.com/patients/about/cause.aspx
http://themedicalbiochemistrypage.org/pompedisease.php
http://www.pompe.com/patients/inheriting-pompe.aspx

Introduction

Hello everyone, welcome to our new blog!!

This blog was created as part of our Medical Biochemistry module project and we have chosen Pompe disease as our subject of interest. So before we dive into the details lets first do a little self introduction to kick start this journey! :D My name is Mei Ying and my project partner is Rose. What can you expect from the both us the next few weeks you say? Well the title of the blog says it all! Every week the both of us will update the blog by posting some interesting facts or details about Pompe disease. Don't worry if you know nothing about the disease at all because that's what this blog is all about, to understand the disease ;) so if you follow us diligently for the next couple of weeks we will keep you on track on what's goin' on :)

Alrighty, now that the self-introduction part is done we shall satisfy the needs of the knowledge-hungry viewers ;).  So what exactly is pompe disease? Pompe disease is a type of glycogen storage disease. Glycogen is a type of complex carbohydrate and it serve as a store of sugar in our body. After you eat a meal for example, the digested food is converted to glucose which enters your bloodstream. When the level of glucose is high in your blood, your body will convert glucose to glycogen and glycogen will be stored in your cells. Usually, the glycogen will be broken down back to glucose for use later but for people suffering from Pompe disease, the break down doesn't happen and glycogen accumulates in the cells. This can cause damage and affect the functions of the organs!

Pompe disease is an inherited disease so it can be passed down generations, but fear not as this disease is also quite rare (with 1 in 40, 000 births in the US).

There are 3 type of this disease : the classic infantile-onset Pompe disease , the non-classic infantile-onset Pompe disease and the late onset Pompe disease.

Both the classic and non-classic infantile-onset disease affects infants while the late-onset disease affects people in their late childhood, adolescents or even adulthood. The infantlile-onset diseases are often fatal but for the late-onset disease the survival rate is higher. More details about each type will be mentioned in a later post, so stay tuned to find out !

That is all for now, we hope that you have gained more insights on the disease and we once again welcome you on board this journey with us! Adieu~

Mei Ying :)