8. Lysosomal diseases (tesaurismoses) Flashcards
What are Storage Diseases?
Diseases DUE to Hereditary Factors
CONNECTED with Metabolism Disturbance
What are the Causes of All Storage Diseases?
Autosomal Recessive
Sex (-X-) Linked Recessive Genetic Transmission
What are MOST Storage Diseases known as?
LYSOSOMAL Storage Diseases
ARISING from Glycogen Storage Diseases
What are Storage Diseases Classified into, According to Type of Metabolism Disturbance?
a. Proteinoses
b. Lipidoses
c. Glucogenoses
What are the MOST Frequent Lipidoses?
- Gaucher’s Disease
2. Niemann-Pick’s Disease
1| What is Gaucher’s Disease?
Autosomal Recessive Disorder
DUE to DEFICIENCY of Lysosomal Enzyme = GLUCOCEREBROSIDASE
1| What does Gaucher’s Disease Lead to?
Lysosomal Accumulation of Glucocerebroside
IN Phagocytes + Neurons
1| What are the 3 Types of Gaucher’s Disease?
a. Type 1 = Classic
b. Type 2 = Infantile
c. Type 3 = Juvenile
1a| What is Type I (Classic) Gaucher’s Disease?
Adult Form
The Storage of Glucocerebrosides IN Phagocytes
Involving Spleen / Liver / BM / Lymph Nodes
1b| What is Type II (Infantile) Gaucher’s Disease?
Where there’s Progressive Involvement of CNS
1c| What is Type III (Juvenile) Gaucher’s Disease?
Features BOTH Type I + Type II
Systemic Involvement (Type I)
Progressive Involvement of CNS (Type II)
1| What are the MICROSOPIC Observations of Gaucher’s Disease?
LARGE N.O of Distended + Enlarged MFs = Gaucher Cells
Single Nucleus / Sometimes 2/3
Cells RICH in Phosphatase
Found in Spleen / Liver / BM / Lymph Nodes / Virchow-Robin Space
2| What is Niemann-Pick’s Disease?
Autosomal Recessive Disorder
DUE to DEFIENCY of SPINGOMYELINASE + Activator Protein
2| What does Niemann-Pick’s Disease Lead to?
Accumulation of Sphingomyelin + Cholesterol
2| When Does Niemann-Pick’s Disease Manifest?
In Infancy
2| What are the 3 Clinical Symptoms of Niemann-Pick’s Disease?
(i) Hepatosplenomegaly
(ii) Lymphadenopathy
(iii) Mental + Physical Retardation
2| What are the MICROSOPIC Observations of Niemann-Pick’s Disease?
SMALLER < than Gaucher Cells
Cytoplasm = Foamy + Vacuolated
Stained (+ve) by FAT STAINS
Located in Spleen / Liver / Lymph Nodes / BM / Lungs / Intestine / Brain
What is the MOST COMMON Disease Among GANGLUISIDOSES?
Tay-Sack’s Disease
What is Tay-Sack’s Disease?
Autosomal Recessive DEFECT
LEADS to Hexosaminidase A DEFICIENCY
What does Tay-Sack’s Disease Lead to?
EXCESSIVE Accumulation of Gangliosides
IN CNS + PNS
LEADS to Progressive Dementia / Hypotonia / Blindness
What are the MICROSOPIC Observations of Tay-Sack’s Disease?
ENLARGED Ganglion Cells
Nuclei PUSHED to Periphery of Cells
What are the MACROSCOPIC Observations of Tay-Sack’s Disease?
Brain Atrophy
Hydrocephaly
Hepatosplenomegaly
What is Hand-Schuller Christian’s Disease, also known as ?
Chronic Disseminated Histioicycosis X
What is Hand-Schuller Christian’s Disease?
Proliferation of Langerhans Cells
FORMING Granulomas
Affecting Sphenoidal Bone (NEXT to Cella Turcica) / Liver / Lymph Nodes
What does Hand-Schuller Christian’s Disease, Lead to?
Diabetes Insipidus
Deafness
Hepatosplenomegaly
Xanthelasmas on Eyelids
What is Glycogenoses?
Glycogen Storage Disease
What are the 3 Glycogenoses Diseases?
- Pompe’s Disease
- McArdle’s Disease
- Von Gierke’s Disease
1| Which is the ONLY Glycogen Storage Disease DUE to Lysosomal Enzyme DEFICIENCY?
Pompe’s Disease
1| What is Pompe’s Disease?
Autosomal Recessive Disorder
DUE to Lysosomal Enzyme DEFICIENCY = ACID MALTASE
RESULTING in Glycogen Accumulation in Heart + Skeletal Muscle
1| What are the Clinical Symptoms of Pompe’s Disease?
Cardiomegaly
Hypotonia
2| What is McArdle’s Disease?
DEFICIENCY of MUSCLE PHOSPHORLYASE
RESULTING in Glycogen Accumulation in Muscle
COMMON in 2nd - 4th Decade in Life
2| What are the Clinical Symptoms of McArdle’s Disease?
Painful Muscle Cramps
AFTER Exercise
3| What is Von Gierke’s Disease?
Autosomal Recessive Disorder
DUE to GLUCOSE-6-PHOSPHATE DEFICIENCY
RESULTING in Glycogen Accumulation in Liver / Hypoglycaemia
3| How does VG’s Disease Cause Hypoglyaemia?
REDUCED Formation of Free Glucose
FROM Glycogen
3| What are the Clinical Symptoms for VG’s Disease?
Hyperlipoproteinemia
Ketosis
DUE to Fat Metabolism FOR Energy!
3| What are the Clinical Symptoms of VG’s Disease in Infancy?
Stunted Growth
ENORMOUS Hepatomegaly w/ Intracytoplasmic + Intranuclear Glycogen
Enlarged Kidneys w/ Intracytoplasmic Glycogen in Tubular Epithelial Cells
Gout
Skin Xanthomas
Haemorrhagic Diathesis DUE to Platelet Dysfunction
What is Mucopolysacchridoses?
Disturbance of Glycosaminoglycans
DUE to Hereditary Factors / Storage Disease
DEFICIENCY of SPECIFIC Lysosomal Enzyme
{FOR Muco-PS Degradation}
What does Mucopolysacchridoses Lead to?
Mucopolysaccharide Accumulation IN
- Mononuclear Phagocytic Cells
- Endothelial Cells
- SM Cells
- Fibroblasts
Where does Mucopolysacchridoses Manifest in?
Infancy
Early Childhood
Affecting = CT / Liver / Spleen / BM / Lymph Nodes / Kidneys / Heart / Brain
What is the MICROSCOPIC Observation for Mucopolysacchridoses ?
Finely Granular
LIGHT Microscopy = PAS (+ve
ELECTRON Microscopy = Swollen Lysosomes
What Disease is Associated with Mucopolysacchridoses ?
Pfaundler-Hurler Disease
Gargoilism
- CONGENITAL DEFECT of Enzyme Determining GAG Metabolism
What are the Clinical Symptoms of Pfaundler-Hurler Disease / Gargoilism?
Irregular Skeleton Growth
MASSIVE Skull
Heart Defects
Inguinal + Umbilical Hernias
Hepato - + Splenomegaly
Keratoleukoma = Retina Opacity
