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GAUCHERS DISEASEPresented by:Alexandra Regilyne M. RomeroHistory of Gaucher Disease1882- Frenchphysician, Philippe CharlesErnest Gaucher (go-SHAY)described a clinical syndrome in a 32 yr. old women whoseliver and spleen wereenlarged.
History of Gaucher Disease1924- German physician, H. Lieb isolated a particular fatty compound from the spleens of people with Gaucher disease.
1934- French physician, A. Aghion identified this compound as glucocerebroside.3History of Gaucher Disease1965- American physician, Roscoe O. Brandy demonstrated that the accumulation of glucocerebroside results from a deficiency of the enzyme glucocerebrosidase.What is Gaucher Disease?Gaucher's disease is caused by a deficiency of the enzyme glucocerebrosidase, which helps the body process the fatty substance glucocerebroside.The disease is sometimes called glucocerebrosidase deficiency.What is Gaucher Disease?People with Gaucher disease lack the normal form of the glucocerebrosidase, and are unable to break down glucocerebroside.Instead, glucocerebroside remains stored within the lysosomes, preventing the macrophages from functioning normally.What is Gaucher Disease?Enlarged macrophages, due to the accumulated glucocerebroside, are known as, Gaucher cells.
The MutationGlucocerebrosidase gene locus 1q21Amino acid substitution of serine for asparagine.Transient expression studies following oligonucleotide-directed mutagenesis of the normal cDNA confirmed that the mutation results in loss of glucocerebrosidase activity.Inheritance PatternsGaucher disease is a autosomal recessive trait.Gaucher carriers have have one normal copy of the glucocerebrosidase gene and one defective copy.Since the trait is autosomal, Males and Females have an equal chance of inheriting the defective gene.Gaucher DiseasesGaucher specialists divide the disease into 3 classifications based on the particular symptoms and course of the disease.
Type 1, Adult Gaucher DiseaseType 2, Infantile Gaucher Disease (Rare)Type 3, Juvenile Gaucher Disease (Rare)Type 1, Adult Gaucher DiseaseMost common form.Defective gene for glucocerebrosidase occurs in 1 in 100,000 people in the general population.More common among Ashkenazi Jews, occurring in 1 in every 850 birthsType 1 SymptomsSplenomegalyHepatomegalyBone diseaseThrombocytopeniaGrowth retardation
Type 1 SymptomsBruising/ BleedingAnemiaFatigueBone pain/ crisisAbdominal pain
Type 2 and Type 3Types 2 and 3 Gaucher disease are known as neuronopathic forms of the disorder because they are characterized by problems that affect the central nervous system.Type 2 Gaucher disease usually causes life-threatening medical problems beginning in infancy. Type 3 Gaucher disease tends to progress more slowly than type 2.Type 2 Symptomsliver and spleen enlargement are apparent by 3 months of age.Individuals usually die before 2 years of age
Type 3 SymptomsLiver and spleen enlargement is variable, and signs of brain involvement such as seizures gradually become apparent.Skeletal irregularitieseye movement disordersSeizuresrespiratory problemsand blood disorders.
TreatmentEnzyme Replacement TherapyBone marrow transplantationSurgery to remove the spleenBlood transfusions
http://apamedcentral.org/Synapse/Data/PDFData/0012AMP/amp-43-1-33.pdfFirst year and 6 months of age, she started to have:Blank staresHepotosplenomegalyThrombocytopenia2 years of agePallor Peticchiae on the chestNo erlenmeyer flask deformity
PATIENT 22 Years of ageEpistaxisPallorBone pains 3 years oldHepatosplenomegalyErlenmeyer flask deformityThrombocytopenia a student performing below average with mild mental retardation.
http://apamedcentral.org/Synapse/Data/PDFData/0012AMP/amp-43-1-33.pdfPATIENT 33 years of ageHematomaHepatosplenomegaly 4 years of ageAnemicThrombocytopenicErlenmeyer flask deformity
Currently an average performing student with mild mental retardation.
http://apamedcentral.org/Synapse/Data/PDFData/0012AMP/amp-43-1-33.pdfResults of treatmentWith enzyme replacement therapy, the hemoglobin values normalized after 8 months for Patient 1 and after 2 months for patient 2 and 3.Platelet counts increased to normal levels after 18 months for patient 1 and 7 months for patient 2.The enlarged liver and spleen have diminished to near normal sizes after 2 years of ERT.The clinical response of bone disease to ERT has been reported to be favorable with the disappearance of bone crises and new fractures under ERT, and marked reduction in the intensity and frequency of bone painReferenceshttp://www.actamedicaphilippina.com.ph/content/genotype-phenotype-correlations-filipino-patients-type-3-gaucher-diseasehttp://www.ninds.nih.gov/disorders/gauchers/gauchers.htmhttp://apamedcentral.org/Synapse/Data/PDFData/0012AMP/amp-43-1-33.pdfhttp://www.gaucherdisease.org/symptoms.php