Diseases Flashcards
(19 cards)
Ehlers-Danlos
Collagen Disease (Types I, III)
Skin, hyperextension of skin
a. Inheritable defects in collagen metabolism (lysil-hydroxylase deficiency; procollagen peptidase deficiency)
b. Mutations in genes for collagen (mostly types I, III)
Osteogenesis Imperfecta/Brittle Bone Disease
Collagen Disease
Mutation in the gene that codes for Type-I Collagen
This deficiency arises from an amino acid substitution of glycine to bulkier amino acids in the collagen triple helix structure.
Bone fragility (with a predisposition to multiple childhood fractures), hearing loss, and a distinctive blue sclera. (BRS 5th)
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(Gly X Y) “X= Proline” “Y= hydroxyproline”
a. Type II= massive fractures
b. a.k.a. brittle bone syndrome
c. mostly mutations of Gly (allows tight packing) → Type I characterized by bulky replacement of Gly
Scurvy
Collagen Disease
Deficiency in Ascorbic Acid (Vitamin C), a necessary cofactor for Collagen production
Vitamin C is necessary to cross-link collagen fibrils (the last step in collagen synthesis)
Vitamin C/Ascorbic Acid is required by the enzymes Prolyl hydroxylase in order to cross-link fibrils.
Prolyl Hydroxylase converts proline in collagen C to hydroxyproline, which stabilizes collagen (Biochem for dummies)
Symptoms: Purple or hemorrhagic oral mucosa, painful thighs, with infants assuming a frog-leg posture for comfort, and subperiosteal hemorrhage of the femur and tibia. (BRS 5e)
Alport Syndrome
Collagen Type IV (Child renal diseases)
Defect in α chain of type IV collagen
Alport syndrome is caused by X-linked mutations, which prevent the proper production or assembly of the type IV collagen network, which is an important structural component of basement membranes in the kidney, inner ear, and eye.
When mutations prevent the formation of type IV collagen fibers, the basement membranes of the kidneys are not able to filter waste products from the blood and create urine normally, allowing blood and protein into the urine.
Characterized by renal failure, nerve deafness, and cataracts. Hematuria is also common.
Emphysema
(α1-antitrypsin deficiency)
Break down of Elastin
α1-antitrypsin = protease inhibitor/stops elastase
a. Made in the liver. Defective antitrypsin forms gobules in liver.
b. Elastase: breaks down elastin - protein that keeps tissues elastic
c. α1-antitrypsin deficiency: results in emphysema (elastin degradation in lungs)
Symptoms: Shortness of breath. People with Emphysema do not get enough Oxygen and have high CO2 in their blood.
Marfan’s Syndrome
FBN1 (Fibrillin 1) Mutation
a. Autosomal Dominant
b. Arachnodactyly, mitral valve prolapsed, chest deformity, displacement of lens in the eye, dilation of the root of the aorta, aordic dissection
c. Caused by fibrillin 1 deficiency.
Mucopolysaccharidoses/GAG diseases
- Glycosaminoglycans (long chain of disaccharide repeats) buildup (degradation now upset)
- Lysosomal disease family (deficiencies of lysosomalglycosidases[i.e. heparin sulfate & dermatan sulfate])
- Undegraded GAG’s appear in urine. (screening)
- Associate with “Gargoylism”
Hurler Syndrome
Most sever of Mucopolysaccharidoses
a. α-L-Iduronidase affected enzyme
b. Autosomal Recessive
c. Corneal clouding
Schie is a less severe form of this syndrome
Hunter’s Syndrome
A less severe Mucopolysaccharidoses
a. Iduronate sulfatase
b. X-Linked Recessive
Sanfilippo Syndrome
Mucopolysaccharidoses
Four types;
severe nervous system disorder
Marateaux-Lamy Syndrome
Mucopolysaccharidoses
a. Buildup of Dermatan Sulfate
b. Arylsulfatase B deficiency
Epidermolysis bullosa simplex (EBS)
Defective keratin (IF types I, II)
Mutated genes encode proteins that cannot co-assemble to form strong IFs.
Symptoms: Skin blisters after minor traumas, excessive keratinization of the epidermis
Laminopathies
Defects in genes coding for:
- Lamin B:
- Emerin
- LBR:
- Lamin A/C
Emery-Dreifuss muscular dystrophy
- *Emerin** and LMNA (Lamin A/C) affected.
a. Nuclear envelope more fragile
b. X-linked or Autosomal dominant
Symptoms: Skeletal muscle and cardiac muscle impairment, joints are restricted
Pelger-Huet anomaly
Defective LBR (Lamin B receptor) and Emerin
Anomaly in blood granulocytes (a type of lymphocyte, or white blood cell)
Lamin B receptor is in the inner membrane of the nuclear envelope and anchors the lamina and the heterochromatin to the membrane. It may mediate interaction between chromatin and lamin B.
Progeria/Hutchinson-Gifford Progeria Syndrome
Mutation of Lamin A (LMNA) gene – resulting in a deficiency of Lamin A.
Rupture of the nuclear envelope and release of chromatin
Symptoms: Premture aging,
as well as premature atherosclerosis and coronary disease, alopecy (hair loss), and bone fractures
Charcot-Marie-Tooth Disease Type 2B1
Defect in Lamin A (LMNA gene)
Autosomal Dominant
Symptoms: Hypotonia, high foot arch, and claw toes
Dilated Cardiomyopathy
Lamin A (LMNA) defect
The heart becomes weakened and enlarged and cannot pump blood efficiently.
The decreased heart function can affect the lungs, liver, and other body systems.
Dunnigan-type Familial Partial Lipodystrophy
Defective Lamins A and C (LMNA gene)
Lose arm fat, gain neck fat
