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

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Jones Andrew 11100364 Gaucher Disease