Genetic Metabolic Disorders Overview

Lysosomal Storage Disorders

• Lysosomal glycogen storage disease: accumulation of glycogen. Degenerative disease of the Central Nervous System
• Tay-Sachs: loss of optic nerve fibers, several neural degenerations
• Accumulation of large amounts of liquids

Mitochondrial Disorders

• Mitochondrial myopathy: degenerative disease of the brain's white matter
• Metabolic disturbances and accumulation of lactic acid
• All are maternally inherited
• MELAS (Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like Episodes)
• MERRF (Myoclonic Epilepsy with Ragged Red Fibers):

Proteosome Disorders

• Alzheimer's disease and Huntington's disease are closely related to the accumulation of proteins inside the cell due to the failure of degeneration by protesomes

Defective Peroxisomal Proteins

• Adrenoleukodystrophy: destroys the myelin sheaths in nerves

Kartagener

• Defect in microtubules (dynein arm mutations) leads to immotile spermatozoa, male infertility and frequent respiratory infections

Hemochromatosis

• Accumulation of iron in hemosiderin
• Hemosiderosis: excessive lysis of red blood cells

### Parkinson's Disease

• Degenerative disease caused by the loss of dopaminergic neurons from the brain's substantiated nigra

Huntington's Chorea

• Hereditary disease caused by the loss of basal ganglia neurons

Multiple Sclerosis

• Disease of the Central Nervous System
• Characterized by a loss of myelin and plaque formation
• Leukocytes (T cells) initiate an inflammatory response
• Loss of Oligodendrocytes and axon demyelination

Guillain–Barré Syndrome

• Autoimmune syndrome of the Peripheral Nervous System
• Immune destruction of Schwann cells results in demyelination and axonal degeneration

Hydrocephalus

• Decrease in the absorption of Cerebrospinal Fluid (CSF) or blockage of outflow from the ventricles leading to an enlarged head
• Mental impairments are possible

AIDS Dementia Complex

• HIV-1 infection of the Central Nervous System
• Infection of microglia
• Replication of HIV-1 in microglia

Metaplasia

• Transformation of one type of epithelial tissue to another
• Respiratory epithelium in heavy smokers can be transformed to stratified squamous epithelium
• Transformation of transitional to squamous epithelium in the bladder

Barrett Esophagus

• In cases of chronic acid reflux, the esophagus is replaced by glandular mucus-secreting epithelium

Epithelial Cell Tumours

• Carcinomas: malignant tumor from surface epithelia
• Adenocarcinomas: malignant tumor from glandular epithelium

Polycystic Kidney Disorder

• Loss of microvilli (brush border) in the small intestine caused by an immune reaction against the wheat protein gluten

Celiac Disease

• Enterotoxin from Clostridium bacteria causes food poisoning
• Enterotoxin binds claudine, resulting in the disruption of tight junctions, diarrhea and intestinal ulcers

Pemphigus vulgaris

• Production of antibodies against the desmosomal proteins leading to widespread skin and mucous membrane blistering

Helicobacter Pylori

• Causes gastric ulcers
• Binds to the extracellular domains of tight junction proteins

Mutation in Connexin Genes

• Causes deafness and peripheral neuropathy

Macrophages in pathological conditions

• When adequately stimulated, they grow and arrange in clusters forming epithelioid cells
• Several may fuse to form multinuclear giant cells

Regenerative Capacity of Connective Tissue

• The spaces left after injury are filled by connective tissue which doesn't divide and forms a scar
• Fibroblasts are the main cell type involved in repair
• Myofibroblasts are responsible for wound contraction

Myeloma

• Multiple Myeloma: tumor of plasma cells in the bone marrow due to accumulation of myeloma cells

Hurler Syndrome

• Accumulation of Glycosaminoglycans
• Accumulation of mucopolysaccharides

Hunter Syndrom

• Accumulation of mucopolysaccharides

Marfan Syndrome

• Defect in fibrillin-1, a protein involved in connective tissue formation.

Duchenne Muscular Dystrophy

• Mutations of the dystrophin gene leading to defective linkages between the cytoskeleton and the extracellular matrix

### Lung Emphysema

• Defect in α1-antitrypsin leads to increased elastase activity
• Elastase damages lung alveoli due to the loss of supporting elastic fibers

Myasthenia Gravis

• Autoimmune disorder that involves circulating antibodies against proteins of acetylcholine receptors
• The extraocular muscles of the eyes are commonly the first affected

Keloid

• Overgrowth of granulation tissue (collagen III) at the site of a healed skin injury which is slowly replaced by collagen type 1

Osteoarthritis

• Degenerative joint disease, reduction of proteoglycan results in reduced intracellular water content in the cartilage matrix, chondrocytes stimulate metalloproteinases which inhibits type II collagen and proteoglycans.

Osteopetrosis

• Dense heavy bones caused by a lack of osteoclastic activity leading to a defect in bone resorption

Osteoporosis

• Imbalance in skeletal turnover, bone resorption exceeds bone formation
• This can be caused by immobilization or postmenopausal women

Osteosarcomas

• Malignant osteoblasts located in the periosteum

Osteomalacia

• Softening of adult bone due to calcium deficiency
• Results in bone fragility and pain

Rickets

• Calcium deficiency in children
• Characterized by bone deformities

Paget Disease

• Increased activity of osteoblasts and osteoclasts leading to weaker than normal bone

This quiz covers various genetic metabolic disorders, including lysosomal storage disorders, mitochondrial disorders, proteosome disorders, and defective peroxisomal proteins. Each topic delves into specific conditions like Tay-Sachs, MELAS, and adrenoleukodystrophy, providing insight into their characteristics and implications. Test your knowledge on these complex genetic conditions and their impact on health.