Download - Jones Andrew 11100364 Gaucher Disease
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Andrew Jones
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History Gaucher Disease
was first identifiedand soon namedafter Dr. Philippe
Charles ErnestGaucher in 1882
Dr. Gaucher was aFrench physician
who noticed aclinical syndromewhile observing theenlarged liver and
spleen of a thirtyear old woman
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History
Gaucher examined the cells of theenlarged spleen which were referred toas Gaucher cells
1924 - H. Lieb, a German physician,isolated a fatty compound from thespleens of patients with the disease
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History Cont. 1934 - Nearly ten years
later, A. Aghion, a Frenchphysician, identified thissusbtance asglucocerebroside (acomponent of the cellmembranes of red andwhite blood cells)
1965 - Americanphysician Roscoe O.
Brandy provided evidenceproving thatglucocerebroside collectsin Gaucher cells due tothe absence or lack of
glucocerebrosidase, anenzyme
Bone marrow in a patient with Gaucher
Disease.
Gaucher cells prevail on the left side asindicated by the arrows.
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Basic Idea Individuals with Gauchar Disease are unable
to breakdown gluococerebroside since theylack the normal form of the
glucocerebrosidase enzyme The glucocerebroside remains stored in the
lysosomes and the macrophages cannotfunction normally
Machrophages that are enlarged consisting ofundigested glucocerebroside are Gauchercells
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Symptoms
Gaucher Disease is classified into three
Types
Type 1: Adult Gaucher Disease
Type 2: Infantile Gaucher Disease
Type 3: Juvenile Gaucher Disease
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Type 1: Adult Gaucher
Disease Type 1 is the only
prevalent form; it is byfar the most common
1/100,000 peopleaffected
However 1/850Ashkenazi Jews areaffected
Most likely to beginduring adulthood
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Common Symptoms
Enlarged spleen and liver
Compression of the lungs
Decreased ability to provide oxygen to theblood
Kidney function is disrupted
Purple/red spots around the eyes Growth retardation in children
Lack of energy and stamina
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Symptoms Cont.
Loss of appetite
Subnormal levels of red and white blood
cells Increased bleeding tendency
Spontaneous fractures
Pain and degeneration of joints Widening of bones, especially along the
knee joint
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Type 2 Gaucher Disease
Fewer than 1/100,000 newborns
Severe neurological involvement during
year 1
Child usually passes away before his or
her second birthday
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Type 3 Gaucher Disease
Just as rare as Type 2, also known as
Juvenile Gaucher Disease
Similar to Type 2, however, neurologicaldamage progresses at a much slower
rate
May survive into their thirties or forties
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How Gaucher Disease
Affects a Family The individual suffering from the diseaseneeds attention
He or she suffers emotionally and socially
due to several factors Some of these factors include, physical pain,
emotional and social problems, fatigue, lackof mobility, appetite, and appearance
All of these differ depending on the severity ofthe individual
Some may have such a minor case that theycan go on with life as if they never had thedisease
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Parents consult their physician to seewhether or not they should restrict theirchilds activity
It is also difficult on deciding when to inform
the child of his or her condition It is sometimes the most difficult when people
with Gaucher Disease discover their firstsymptoms in adulthood
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Programs
Organizations such as the National GaucherFoundation provide support to those who suffer fromthis complex disease
They help patients through means of financial aid,while they have exercises, approved treatments, andmany other resources
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Causes
Generally speaking, Gaucher Disease occursas a result of the deficit of theglucocerebrosidase enzyme
This enzyme is suppose to break down fattysubstances, or lipids known asglucocerebrosides
Since there is a lack of this enzyme in peoplewith Gaucher Disease, fatty substances buildup in the brain, bone marrow, and otherorgans
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Causes Cont.
A Mutationoccurs on theglucocerebrosidase gene locus 1q21
Single base mutation in exon 9 of theglucocerebrosidase gene
In the adenosine to guanosine transition
Amino acid substitution of serine for
asparagine
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Treatment:Enzyme
Replacement Therapy Dr. Roscoe Brady assisted in the
development of this therapy at the NationalInstitute of Neurological Disorders and Stroke
Modified glucocerebrosidase enzyme(Ceredase) provides evidence that afterrepeated infusions, symptoms are reducedand the disease progression is impeded
This can be used for Types 1 and 3
Type 2 basically has no treatment
Ceredase received FDA approval in 1992
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More Recent Treatment
The altered glucocerebrosidase enzymeis now using a recombinant cell line
It is called Cerezyme and received FDAapproval in 1996
Ceredase has more or less been
replaced by this product Approximately 4000 people with thedisease use this therapy today
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Identification of the
Disease/Diagnosis Gaucher Disease is most often discovered
when patients express symptoms of the
disease Physicians are notified if there is a family
history
If laboratory analysis indicates elevated levels
of acid phosphate in the blood serum, or
abnormal skeletal features revealed in x-rays,
the disease may be identified
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If these symptoms strongly suggest apresence of Gaucher Disease, bloodwork will be done
Physicians will look for a decreasedactivity level of glucocerebrosidase inwhite blood cells
Bone marrow may be used for testing
as well
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How it may affect their
offspring Defective glucocerebrosidase gene can be
passed on to both male and females
Gaucher Disease is an autosomal recessivedisorder
An individual must inherit two defective(homozygous recessive) copies of the gene,
one from each parent For a child to develop the disease, bothparents must be carriers
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If only one parent is
a carrier, none of
the offspring willinherit the disease
However there is a
50% chance that the
children will becarriers
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Four Other Scenarios
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Bioethical Considerations Because this disease is very rare, it is no
where near as prominent in discussion asother diseases which we witness inindividuals everyday, such as Downs
syndrome or cerebral palsy However, it is vital that we treat individuals
who suffer not from just Gaucher Disease, butfrom all sicknesses, just as we want to be
treated It is very difficult to live life with Gaucher
Disease as it is unpredictable, and for some,symptoms do not arise until adulthood
These scenarios are simply tragic
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Sources
Photos http://bloodjournal.hematologylibrary.org/content/105/12/4
546/F1.expansion
http://upload.wikimedia.org/wikipedia/commons/thumb/7/7e/Philippe_Charles_Ernest_GAUCHER.jpg/220px-Philippe_Charles_Ernest_GAUCHER.jpg
http://drugline.org/img/ail/2532_2550_1.jpg
http://sphotos-a.xx.fbcdn.net/hphotos-ash3/546622_10150888077372264_1441221755_n.jpg
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Sources "Living with Gaucher Disease: A Guide for Patients,
Parents, Relatives and Friends" Gaucher Disease: AGuide for Patients. Wisebury Publications, 1991.Web. 27 Feb. 2013.
Grabowski GA, Andria G, Baldellou A, Campbell PE,Charrow J, Cohen IJ, Harris CM, Kaplan P, MengelE, Pocovi M, Vellodi A. Pediatric non-neuronopathicGaucher disease: presentation, diagnosis andassessment. Consensus statements. Eur J Pediatr.2004 Feb;163(2):58-66. Epub 2003 Dec 16. Review.
Sidransky E. Gaucher disease: complexity in asimple disorder. Mol Genet Metab. 2004 Sep-Oct;83(1-2):6-15. Review.
Jmoudiak M, Futerman AH. Gaucher disease:pathological mechanisms and modern management.
Br J Haematol 2005 Apr;129(2):178-88 Review