Archives for May 2009

GBA gene (glucosidase, beta; acid)

8 May by Mommy

http://ghr.nlm.nih.gov/gene=gba

What is the official name of the GBA gene?

The official name of this gene is “glucosidase, beta; acid (includes glucosylceramidase).”

GBA is the gene’s official symbol. The GBA gene is also known by other names, listed below.

What is the normal function of the GBA gene?

The GBA gene provides instructions for making an enzyme called beta-glucocerebrosidase. This enzyme is active in lysosomes, which are structures inside cells that act as recycling centers. Lysosomes use digestive enzymes to break down toxic substances, digest bacteria that invade the cell, and recycle worn-out cell components. Based on these functions, enzymes in the lysosome are sometimes called housekeeping enzymes. Beta-glucocerebrosidase is a housekeeping enzyme that helps break down a large molecule called glucocerebroside into a sugar (glucose) and a simpler fat molecule (ceramide).

How are changes in the GBA gene related to health conditions?

Gaucher disease – caused by mutations in the GBA gene
More than 200 mutations in the GBA gene have been identified in people with Gaucher disease. These mutations occur in both copies of the gene in each cell. Most of the GBA mutations responsible for Gaucher disease change a single protein building block (amino acid) in beta-glucocerebrosidase, altering the structure of the enzyme and preventing it from working normally. Other mutations delete or insert genetic material in the GBA gene or lead to the production of an abnormally short, nonfunctional version of the enzyme.

Mutations in the GBA gene greatly reduce or eliminate the activity of beta-glucocerebrosidase in cells. As a result, glucocerebroside is not broken down properly. This molecule and related substances can build up in white blood cells called macrophages in the spleen, liver, bone marrow, and other organs. Tissues and organs are damaged by the abnormal accumulation and storage of these substances, causing the characteristic features of Gaucher disease.

Parkinson disease – associated with the GBA gene
Growing evidence suggests an association between GBA mutations and Parkinson disease or Parkinson-like disorders that affect movement and balance (parkinsonism). People with Gaucher disease have mutations in both copies of the GBA gene in each cell, while those with a mutation in just one copy of the gene are called carriers. Some studies suggest that people with Gaucher disease and GBA mutation carriers have an increased risk of developing Parkinson disease or parkinsonism.

Symptoms of Parkinson disease and parkinsonism result from the loss of nerve cells that produce dopamine. Dopamine is a chemical messenger that transmits signals within the brain to produce smooth physical movements. It remains unclear how GBA mutations lead to these disorders. Researchers speculate that GBA mutations may contribute to the faulty breakdown of toxic substances in nerve cells by impairing the function of lysosomes, or mutations may enhance the formation of abnormal protein deposits. As a result, toxic substances or protein deposits could accumulate and kill dopamine-producing nerve cells, leading to abnormal movements and balance problems.

other disorders – associated with the GBA gene
Emerging research suggests an association between GBA mutations and a disorder called dementia with Lewy bodies. Lewy bodies are abnormal deposits of the protein alpha-synuclein that form in some dead or dying nerve cells. Specifically, they occur in nerve cells that produce a chemical messenger called dopamine. The features of this disorder are variable, but symptoms typically include a loss of intellectual functions (dementia), visual hallucinations, and fluctuations in attention. Affected individuals may also experience changes that are characteristic of Parkinson disease such as trembling or rigidity of limbs, slow movement, and impaired balance and coordination.

People with mutations in both copies of the GBA gene in each cell develop Gaucher disease, while those with a mutation in just one copy of the gene are called carriers. Research suggests that carriers have an increased risk of developing dementia with Lewy bodies, although it remains unclear how GBA mutations increase this risk. Researchers speculate that GBA mutations can alter the structure of beta-glucocerebrosidase and impair the function of lysosomes. As a result, alpha-synuclein may not be processed properly, allowing the formation of Lewy bodies.

Where is the GBA gene located?

Cytogenetic Location: 1q21

Molecular Location on chromosome 1: base pairs 153,470,866 to 153,481,111
The GBA gene is located on the long (q) arm of chromosome 1 at position 21.

The GBA gene is located on the long (q) arm of chromosome 1 at position 21.

More precisely, the GBA gene is located from base pair 153,470,866 to base pair 153,481,111 on chromosome 1.

See How do geneticists indicate the location of a gene? in the Handbook.

Where can I find additional information about GBA?

You and your healthcare professional may find the following resources about GBA helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the GBA gene or gene products?

  • Acid beta-glucosidase
  • Alglucerase
  • beta-D-glucosyl-N-acylsphingosine glucohydrolase
  • Beta-glucocerebrosidase
  • D-Glucosyl-N-acylsphingosine glucosylhydrolase
  • GBA1
  • GLCM_HUMAN
  • GLUC
  • Glucocerebrosidase
  • Glucocerebroside beta-Glucosidase
  • glucosphingosine glucosylhydrolase
  • Glucosylceramidase
  • Glucosylceramide beta-Glucosidase
  • Imiglucerase

See How are genetic conditions and genes named? in the Handbook.

Where can I find general information about genes?

The Handbook provides basic information about genetics in clear language.

These links provide additional genetics resources that may be useful.

What glossary definitions help with understanding GBA?

acids ; amino acid ; bacteria ; bone marrow ; carrier ; cell ; ceramides ; dementia ; digestive ; dopamine ; enzyme ; gene ; glucose ; hallucinations ; Lewy bodies ; lysosome ; macrophage ; molecule ; mutation ; nerve cell ; parkinsonism ; protein ; symptom ; tissue ; toxic ; white blood cells

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.

See also Understanding Medical Terminology.

References (14 links)
~ Filed Under: Gaucher's Disease Tagged With: ,

Another type 2 little girl…

7 May by Mommy

I met this mom online just a few weeks ago.  Her 7-month-old daughter was just diagnosed with neuronopathic Gaucher’s disease.  They weren’t sure of which type, type 2 or type 3.  They got the results today — type 2. 

I haven’t been able to stop thinking about her, her mom, and her two older siblings who are even younger than Ethan and Abigail.  They are living my nightmare that I’m praying to avoid, yet many times feel may be inevitable.   This just shouldn’t be happening!

Why can’t we get more people to realize how devastating this disease is and work with us to help us find even just a treatment to help slow the disease down!   Unlike the “big diseases” who have millions and millions poured into them to find a cure or treatment without success, we haven’t even been given a chance to really look for a treatment. 

Without awareness, there is no funding. 
Without funding, there is no research. 
Without research, our kids die. 
Our kids deserve a fighting chance.

This little girl, whom I have never met, rejuvenated my drive to continue to fight after these past two crappy days of feeling beat and defeated.  She is just two months younger than Hannah.  I’m not giving up on this, I just can’t.

~ Filed Under: Hannah's Fight Tagged With:

Calcium signaling in neurodegeneration

7 May by Mommy

http://www.molecularneurodegeneration.com/content/4/1/20

Calcium is a key signaling ion involved in many different intracellular and extracellular processes ranging from synaptic activity to cell-cell communication and adhesion. The exact definition at the molecular level of the versatility of this ion has made overwhelming progress in the past several years and has been extensively reviewed.

In the brain, calcium is fundamental in the control of synaptic activity and memory formation, a process that leads to the activation of specific calcium-dependent signal transduction pathways and implicates key protein effectors, such as CaMKs, MAPK/ERKs, and CREB. Properly controlled homeostasis of calcium signaling not only supports normal brain physiology but also maintains neuronal integrity and long-term cell survival.

Emerging knowledge indicates that calcium homeostasis is not only critical for cell physiology and health, but also, when deregulated, can lead to neurodegeneration via complex and diverse mechanisms involved in selective neuronal impairments and death. The identification of several modulators of calcium homeostasis, such as presenilins and CALHM1, as potential factors involved in the pathogenesis of Alzheimer’s disease, provides strong support for a role of calcium in neurodegeneration.

These observations represent an important step towards understanding the molecular mechanisms of calcium signaling disturbances observed in different brain diseases such as Alzheimer’s, Parkinson’s, and Huntington’s diseases.

~ Filed Under: Gaucher's Disease Tagged With: , , ,

What to say?

7 May by Mommy

I really don’t know what to talk about tonight.  I can talk about how much we learned during her PT evaluation this morning or how much we enjoyed our developmental therapy or the informative conversation I had with Dr. Greg Grabowski this afternoon or Abigail getting into a fight at school or Scrubs ending its series after 8 years (one of my favorite shows) or still reeling from the disappointment with the failure of a Hannah Mouse or getting some very upsetting news about a partnership that was “in the works.”

I don’t know, just not feeling like elaborating tonight.

The only thing I still have in my mind is Dr. Grabowski’s comments that based on Hannah’s symptoms and presentation, he felt that she was most likely a “type 2” baby, but that I shouldn’t consider it as a “type” but more of Hannah having a “Hannah’s Gaucher’s Disease” and it is what it is.  

Yet, all I keep in my mind are his words “type 2.”  Life expectancy no more than 2 years… It isn’t anything different than Dr. Schiffmann told us of a “slow type 2 or a severe type 3” but for some reason, I had put that out of my mind.  I keep thinking she is doing so well.  I still feel she is doing so well.

Reality check, I guess.  If there is no treatment found, she will be taken away from us at any time.  At any time, she could start the “snowball effect” of symptoms. 

Why can’t I find something to help her?!

~ Filed Under: Hannah's Fight

Platelets on the rise…

6 May by Mommy

In the midst of all the chaos with the Hannah mouse that couldn’t be, we did receive some good news.

We received Hannah’s platelet count.  149,000!  This is the highest it has ever been, as she had been hovering between 93,000 and 106,000 during the four months before her Cerezyme treatment started.  I just have to believe that the Cerezyme is having some affect because of this!

Anyway, we are off to her PT (physical therapy) evaluation at TCH to see if we need to add additional therapy to what ECI provides.  I’m curious to see what they recommend.  We don’t have the OT (occupational therapy) or ST (speech therapy) evaluations until June.  Which stinks, because we really need to get working on her solid food issues, as we have made no progress in that.

~ Filed Under: Hannah's Fight Tagged With: ,

The “Hannah Mouse” roller coaster

6 May by Mommy

Today was one of those days with incredible highs and subsequent crashing down.

Our family was given an amazing, incredible gift today.  A local biopharmaceutical company had offered to create a “Hannah Mouse” for us, a genetically modified research mouse with Hannah’s unique DNA mutation.  This was HUGE!   The generosity of this company was so enormous, as creating a mouse like this is an expensive, complex, and time-consuming process (about a year or so).  

The VP that I had been working with was such a sweet man, and he contacted me multiple times to share different things he had be learning.  You could tell that he was really researching deep into this project. 

However, after hearing back from Dr. Weinreb (Hannah’s guardian angel) and talking to Dr. Sidransky at the NIH, this had been tried before by Dr. Grabowski (another leading GD23 expert) with not the results they were hoping for.  I have an email into Dr. Grabowski to have this explained in more detail in “mom terms”, but as Dr. Weinreb explained, creating the mouse model may not be easy or even possible. Even some so called mild human mutations are lethal in mouse models and that may be even more likely with a severe mutation like Hannah has.  Apparently, a “Hannah mouse” just is not possible.

Crash…

This would have been a huge boost in our fight for Hannah’s life, as it would give researchers a mouse model to test possible treatments against.  Now, we are back to square one — with this very accessible and forwarding pushing research tool in fighting disease closed to us…

Friggin’ sucks…

~ Filed Under: Hannah's Fight Tagged With:
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