Andrew Jones

Gaucher Disease was first identified and soon named after Dr. Philippe Charles Ernest Gaucher in 1882 Dr. Gaucher was a French physician who noticed a clinical syndrome while observing the enlarged liver and spleen of a thirty year old woman

History

History
Gaucher examined the cells of the enlarged spleen which were referred to as Gaucher cells 1924 - H. Lieb, a German physician, isolated a fatty compound from the spleens of patients with the disease

History Cont.
1934 - Nearly ten years later, A. Aghion, a French physician, identified this susbtance as glucocerebroside (a component of the cell membranes of red and white blood cells) 1965 - American physician Roscoe O. Brandy provided evidence proving that glucocerebroside collects in Gaucher cells due to the absence or lack of glucocerebrosidase, an enzyme

Bone marrow in a patient with Gaucher Disease. Gaucher cells prevail on the left side as indicated by the arrows.

Basic Idea
Individuals with Gauchar Disease are unable to breakdown gluococerebroside since they lack the normal form of the glucocerebrosidase enzyme The glucocerebroside remains stored in the lysosomes and the macrophages cannot function normally Machrophages that are enlarged consisting of undigested glucocerebroside are Gaucher cells

Symptoms
Gaucher Disease is classified into three Types Type 1: Adult Gaucher Disease Type 2: Infantile Gaucher Disease Type 3: Juvenile Gaucher Disease

Type 1: Adult Gaucher Disease

Type 1 is the only prevalent form; it is by far the most common 1/100,000 people affected However 1/850 Ashkenazi Jews are affected Most likely to begin during adulthood

Common Symptoms
Enlarged spleen and liver Compression of the lungs Decreased ability to provide oxygen to the blood Kidney function is disrupted Purple/red spots around the eyes Growth retardation in children Lack of energy and stamina

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

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

Type 3 Gaucher Disease

Just as rare as Type 2, also known as Juvenile Gaucher Disease Similar to Type 2, however, neurological damage progresses at a much slower rate May survive into their thirties or forties

How Gaucher Disease Affects a Family

The individual suffering from the disease needs attention He or she suffers emotionally and socially due to several factors Some of these factors include, physical pain, emotional and social problems, fatigue, lack of mobility, appetite, and appearance All of these differ depending on the severity of the individual Some may have such a minor case that they can go on with life as if they never had the disease

 Parents consult their physician to see whether or not they should restrict their childs 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 first symptoms in adulthood

Programs

Organizations such as the National Gaucher Foundation provide support to those who suffer from this complex disease They help patients through means of financial aid, while they have exercises, approved treatments, and many other resources

Causes
Generally speaking, Gaucher Disease occurs as a result of the deficit of the glucocerebrosidase enzyme This enzyme is suppose to break down fatty substances, or lipids known as glucocerebrosides Since there is a lack of this enzyme in people with Gaucher Disease, fatty substances build up in the brain, bone marrow, and other organs

Causes Cont.
A Mutation occurs on the glucocerebrosidase gene locus 1q21 Single base mutation in exon 9 of the glucocerebrosidase gene In the adenosine to guanosine transition Amino acid substitution of serine for asparagine

Treatment:Enzyme Replacement Therapy

Dr. Roscoe Brady assisted in the development of this therapy at the National Institute of Neurological Disorders and Stroke Modified glucocerebrosidase enzyme (Ceredase) provides evidence that after repeated infusions, symptoms are reduced and 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

More Recent Treatment

The altered glucocerebrosidase enzyme is now using a recombinant cell line It is called Cerezyme and received FDA approval in 1996 Ceredase has more or less been replaced by this product Approximately 4000 people with the disease use this therapy today

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

 If these symptoms strongly suggest a presence of Gaucher Disease, blood work will be done Physicians will look for a decreased activity level of glucocerebrosidase in white blood cells Bone marrow may be used for testing as well

How it may affect their offspring

Defective glucocerebrosidase gene can be passed on to both male and females Gaucher Disease is an autosomal recessive disorder An individual must inherit two defective (homozygous recessive) copies of the gene, one from each parent For a child to develop the disease, both parents must be carriers

 If only one parent is a carrier, none of the offspring will inherit the disease However there is a 50% chance that the children will be carriers

Four Other Scenarios

Bioethical Considerations
Because this disease is very rare, it is no where near as prominent in discussion as other diseases which we witness in individuals everyday, such as Downs syndrome or cerebral palsy However, it is vital that we treat individuals who suffer not from just Gaucher Disease, but from 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

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/220pxPhilippe_Charles_Ernest_GAUCHER.jpg http://drugline.org/img/ail/2532_2550_1.jpg http://sphotos-a.xx.fbcdn.net/hphotosash3/546622_10150888077372264_1441221755_n.jpg

Sources
"Living with Gaucher Disease: A Guide for Patients, Parents, Relatives and Friends" Gaucher Disease: A Guide 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, Mengel E, Pocovi M, Vellodi A. Pediatric non-neuronopathic Gaucher disease: presentation, diagnosis and assessment. Consensus statements. Eur J Pediatr. 2004 Feb;163(2):58-66. Epub 2003 Dec 16. Review. Sidransky E. Gaucher disease: complexity in a simple disorder. Mol Genet Metab. 2004 SepOct;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.