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Diseases associated with Collagen structure Scurvy Osteogenesis Imperfecta Ehler Danlos syndrome Alport syndrome Fuch’s dystrophy Menke’s disease Goodpasture.

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Presentation on theme: "Diseases associated with Collagen structure Scurvy Osteogenesis Imperfecta Ehler Danlos syndrome Alport syndrome Fuch’s dystrophy Menke’s disease Goodpasture."— Presentation transcript:

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2 Diseases associated with Collagen structure Scurvy Osteogenesis Imperfecta Ehler Danlos syndrome Alport syndrome Fuch’s dystrophy Menke’s disease Goodpasture syndrome 2

3 Scurvy 3

4 2/3 rd of Vasco di Gama’s sailors had died due to Scurvy by the time he reached India. 4

5 Scurvy Barlow’s disease. Vitamin C is required for collagen synthesis Hydroxylation of lysine and proline. Lysyl and prolyl hydroxylase. Important for stabilizing pro-collagen peptides. Bleeding gums, joints-hemarthrosis, fragile blood vessels. 5

6 Osteogenesis Imperfecta Brittle bone disease Lobstein disease. Type-1 collagen disease. 6

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8 Osteogenesis Imperfecta Autosomal Dominant disease. Substitution of Glycine with bulkier aminoacids. Larger side chains-Steric hinderance between the chains causing bulges Body hydrolyses the improper collagen structure. 8

9 Signs and Symptoms Blue sclerae, short stature, hearing loss, respiratory problems, dentiogenesis imperfecta Brittle bone – multiple fractures on mild pressure 9

10 Stress state within collagen fibrils is altered at the locations of mutations 10

11 MULTIPLE FRACTURES 11

12 8 TYPES OF OI 12

13 13 Type 1 – mildest form Type 2 – lethal Type 4 – no blue sclera (the blue-gray color of the sclera is due to the underlying choroidal veins which show through the thin sclera) Blue sclerae, short stature, hearing loss, respiratory problems, dentiogenesis imperfecta Brittle bone – multiple fractures on mild pressure

14 Cutis hyperplastica. 14

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17 Ehler Danlos syndrome: Group of genetic defects involving synthesis of collagen(COL5A, COL 3A) and associated proteins. Collagen in connective tissue helps tissues to resist deformation (decreases its elasticity) – due to defect in collagen synthesis  hyperelastic 17

18 Classification: Hypermobility – tenascin gene Type 3 defect This gene encodes a member of the tenascin family of extracellular matrix glycoproteins.Here collagen density is also reduced. Classical – (type1 and 2) affects collagen type 5. Vascular- type 3 collagen 18

19 Clinical features: Hypermobility of the joints Hyperelastic skin Fragile tissue – easy bruising, scaring, wounding. 19

20 Alport syndrome: (Hereditary Nephritis ) X-linked recessive. May be Autosomal recessive. Glomerulonephritis, Deafness Hematuria. Type 4 collagen defect. IMPROPER Basement membrane – basket weave appearance Sensorineural hearing loss. Alport syndrome is caused by mutations in COL4A(n) COL4A3, COL4A4, and COL4A5, collagen biosynthesis genes

21 Fuchs Corneal dystrophy Degenerative disorder of corneal endothelium. Defect in collagen –type 8. Autosomal dominant Fuchs' endothelial dystrophy, is a slowly progressing corneal disease that usually affects both eyes Females>Male 21

22 Fuchs Corneal dystrophy Blurred vision that will gradually clear during the day Later stages - Swelling will remain constant and reduce vision throughout the day. CORNEAL OEDEMA and LOSS of VISION 22

23 Menkes disease Kinky hair disease or menke kinky hair syndrome Mutations in the ATP7A gene on chromosome Xq13 X- linked recessive 23

24 Menke’s disease Copper accumulates in some tissues, such as the small intestine and kidneyssmall intestinekidneys The decreased supply of copper reduce the activity of numerous copper-containing enzymes - lysyl oxidase.enzymes coarse hair, growth failure, and deterioration of the nervous system 24

25 Goodpasture syndrome: Anti-glomerular basement membrane antibody disease. Auto-immune reaction against goodpasture antigen. Glomerulonephritis and hemorrhage of the lungs. 25

26 Goodpasture syndrome: Sometimes this disorder is triggered by a viral respiratory infection or by breathing in hydrocarbon solvents- Type II hypersensitivity reaction to Goodpasture’s antigens on the basement membrane of lungs and kidney. Produces IgG antibo dies against Alpha-3 chain of Type IV collagen. clinical features- cough, hemoptysis, Hematuria, Renal failure 26

27 Marfan syndrome : Autosomal dominant disease Mutation in geneFBN1 encoding for fibrillin protein. Fibrillin also regulates TGF-β. Defect causes abnormalities in lungs, aorta and heart valves. Lens dislocation – supero temporal 27

28 Clinical features: Arachnodactyly – long and slender fingers. Uppersegment longer than lower segment. Scoliosis and pectus excavatum/carinatum. Mitral valve prolapse / aortic regurgitation/ aortic aneurysms. Lungs – spontaneous pneumothorax. 28

29 Alpha -1 antitrypsin deficiency Autosomal co-dominant/ recessive SERPINA1 gene –mutation Either decrease or abnormal synthesis. Allelles – MM-Normal SS- Intermediate ZZ- worst. Neutrophil elastase – damages lungs. 29

30 Clinical features: Development of emphysema Clinical features: difficulty in breathing, wheezing, shortness of breath, respiratory infections, barrel shaped chest. development of Cirrhosis: jaundice, portal hypertension – swollen abdomen, swollen limbs. 30

31 Pseudoxantoma elasticum Pseudoxanthoma elasticum is a progressive disorder that is characterized by the accumulation of deposits of calcium and other minerals (mineralization) in elastic fibers, which are a component of connective tissue. Autosomal recessive ABCC6 gene Chromosome 16 Grönblad–Strandberg syndrome 31 Angioid streaks

32 Features fragmentation and mineralization of elastic fibers in some tissues. Small, yellowish papular lesions –axillae, neck, groin, elbow, knee. dimpling of the Bruch membrane - peau d'orange appearance.Bruch membrane Angioid streaks – calcification of blood vessels. CAD and MI 32

33 MCQ 1 A 4 month old infant who failed to grow and appeared to be mentally retarded was brought to the clinic for testing.The physician noted that the infant had abnormally kinky and hypopigmented hair. Arteriograms showed tortuosity of the major arteries. Blood test showed that the infant had low serum ceruloplasmin and only 10% of normal copper levels. What is the clinical disorder? 1)Osteogenesis imperfecta 2)Scurvy 3) Menke’s disease 4)Blue baby syndrome 5)Phenylketonuria 33 Menke’s disease

34 34

35 35 EXTRA CELLULAR CLEAVAGE

36 36 Marfan’s Syndrome


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