Term
Adrenoleukodystrophy (ALD) |
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Definition
| In ALD, peroxisomes are unable to β-oxidize very long-chain fatty acids, which then accumulate and cause severe neurological problems, including spinal cord dysfunction, weakness/numbness of limbs, and problems with urination and defecation. |
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Term
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Definition
| buildup of Tau protein within neurons,β-amyloid plaque outside; possibly a 'malfunction' disease resultant from a mutation or deletion of a gene, resulting in progressive neuropathies. Receptors for Advanced Glycosylation End Products (RAGE) have also been implicated in Alzheimer's. Patients often experience confusion, problems with short-term memory, personality changes, mood swings, problems with temporal-spatial orientation, and language difficulties. Misfolded proteins aggregate, and the processes that destroy these proteins are inhibited. |
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Term
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Definition
| bullous pemphigoid is an autoimmune skin disease. Blisters form below the surface of the skin and antibodies against the collagen of hemidesmosomes (bp230, BP180 (aka collagen 18), laminin V, and β4 integrin are recognized as foreign and subjected to attack by antibody in bullous pemphigoid) |
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Term
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Definition
| cancerous cells will contain very high concentrations of ER, indicating high levels of activity. |
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Term
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Definition
| the following result from defects in cilia: situs inversus (reversed organ placement), polycystic kidney disease, smoker's cough, immotile sperm, no cilliary movement in fallopean tubes |
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Term
| Charcot-Marie Tooth disorder |
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Definition
| a laminopathy, much like Emery-Dreyfus Muscular Dystrophy - resulting from a mutation in the nuclear lamin A, Charcot-Marie Tooth disorder consists of neuropathy of peripheral nerves, affecting the extremities. Symptoms resemble those of ALS |
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Term
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Definition
a mutation in the CF transmembrane conductance regulator prevents binding with COP II, which doesn't allow the ion channel to reach the golgi. The CFTR ion channel is important in creating sweat, digestive juices, and mucus (all lacking in CF). In Cystic Fibrosis, there is a primary deletion at position 509 coupled with the incorrect degradation of proteins. Exocrine gland dysfunctions lead to the formation of viscous mucous, which then clogs the ducts. If bronchi or bronchioles are obstructed by this thickened mucous, pulmonary infections can result. CF also affects the exocrine glands of the pancreas, leading to a deficiency of pancreatic lipases and bile duct obstruction, which prevents the absorption of fat-soluble vitamins |
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Term
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Definition
resistin has been shown to be a hormone present in adipocytes that inhibits the effects of insulin. Diabetes' advanced glycosylation end products cause the lamina densa to become much thicker, which is especially prevalent in the glomerulus. During normal wound healing, fibroblasts fill from a matrix of Type III collagen and secrete EN-RAGE, which will bind to RAGE and attract immune cells to the site of the wound. In diabetes, AGE binds to the EN-RAGE receptor and prevents proper healing of the wound. Type I diabetics are prone to develop ketoacidosis due to their low insulin levels, which increases fatty acid release from adipose tissue. This causes increased ketone synthesis in the liver, and the body begins to utilize ketone products
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Term
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Definition
| P-glycoprotein (MDR1) normally functions as a floppase for phospholipids and glycosphingolipids, but if overexpressed, can lead to resistance in cancer cells to doxorubicin, Taxol, and etoposide. MDR1 is an ABC transporter. MDR transporters will nonspecifically transport lipophilic, planar molecules out of cells, may have evolved to protect against toxins, and MDR transporters can be upregulated to transport drugs. |
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Term
Duchenne muscular dystrophy |
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Definition
| resulting from a defect in dystrophin. Found in muscles, it binds actin filaments to the sarcolemmal membrane of muscle cells (analogous to the plasma membrane). When they are either absent or non-functional, Duchenne's muscular dystrophy is the result as the muscles are unable to handle stress due to the lack of binding of the cellular cytoskeleton and the proteins of the extracellular matrix. |
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Term
| Emery-Dreyfus Muscular Dystrophy (EDMD) |
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Definition
| EDMD results in a mutation in either emerin (links lamins to the NE) or lamin A, causing the nuclear membrane to lose much of its structural integrity, which prevents desmin from having a firm anchor between skeletal muscle tissue and the nucleus. This allows the muscle to shear away, resulting in dystrophy |
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Term
Epidermolysis bullosa simplex |
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Definition
| a disruption in either transmembrane proteins or proteins anchoring the cell to the plaque of the basal layer, allowing the cell to be 'sluffed off' with little mechanical effort. This causes blistering and open sores due to the defective keratins K5 and K14. Keratins must be paired (alpha, an acidic protein with beta, a basic), and a mutation in either subunit will cause a break down of the structural integrity of the filament, disrupting the anchoring of the cells to the basal lamina. Especially in infants, the sores can be so prevalent and precocious as to cause death from infection. This is a disease involving intermediate filaments |
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Term
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Definition
| A point mutation in the hemoglobin molecule leads to anemia. It is very rare (<10 cases known) and prevents cooperativity in the binding of heme molecules (causing the oxygen-binding curve to become more linear/decrease slope) |
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Term
Familiar hypertrophic cardiomyopathy |
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Definition
| mutations in β-myosin and seven other genes of the myofibrillar apparatus result in familiar hypertrophic cardiomyopathy |
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Term
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Definition
| a lack of glucocerebrocidase. Fatty material can collect in the spleen, liver, kidneys, lungs, brain and bone marrow. |
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Term
Glycogen Storage Diseases (general) |
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Definition
Von Gierke's Disease*, Pompe's Disease*, Cori's disease, Andersen's disease, McArdle's syndrome, and Hers' Disease |
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Term
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Definition
| mutation in melanophilin or RAB27 (attached to myosin V) leads to partial albinism, neurological problems, and sometimes immunodeficiency |
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Term
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Definition
| one cause of hemolytic anemia is a lack of pyruvate kinase. Low ATP leads to a decreased activity of the Na+/K+ pump, which prevents the electrochemical gradient from being properly established. This leads to an osmotic irregularity, which then causes water to rush into red blood cells, causing them to lyse. |
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Term
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Definition
| Hurler syndromeperoxisomes, lysosomes, mitochondria 08.12.2008 is a genetic disorder that results in the buildup of mucopolysaccharidesdue to a deficiency of α-L iduronidase, an enzyme responsible for the degradation of mucopolysaccharides in lysosomes. Without this enzyme, a buildup of heparan sulfate and dermatan sulfate occurs in the body. |
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Term
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Definition
| due to a lack of Mannose-6-phosphate receptors on the golgi, vesicles destined for lysosomes are not properly labeled and the vesicle's contents are released into the bloodstream. Patients often die at less than one year of life due to congestive heart failure or respiratory complications |
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Term
Junctional Epidermolysis Bullosa |
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Definition
| deficiencies in laminin V or collagen VIIcell-matrix interactions 08.13.2008 lead to a shearing of epithelial cells, causing several sores which can be fatal in infants |
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Term
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Definition
| after damage is inflicted to epithelial tissue, fibroblasts produce collagen III in the afflicted area. In normal processes, this collagen is cleared and replaced with collagen I, but this does not occur in keloid. Collagen is produced in excess, and the smooth 'bump' forms as a result. Keloids are more prevalent in blacks and those of Mediterranean descent |
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Term
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Definition
| Kwashiorkor is the result of a deficient intake of proteins. Patients suffer from edema because of the lack of albumin (a water-soluble protein) in the blood, creating an osmotic imbalance. Instead of having the albumin present in the blood to draw water into the vessels, the vessels lose their water to the surrounding tissue, resulting in edema |
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Term
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Definition
| deletions/mutations in the lamins within the nuclear membrane can result in disorders involving skeletal muscle, cardiac muscle, and neural tissue. These include EDMD and Charcot-Marie Tooth Disorder (type II) |
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Term
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Definition
| mutations in dynein/dynactin result in impaired brain development |
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Term
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Definition
| Associated with sudden death, especially in athletes, it is associated with sodium channels not closing properly within cardiac tissue. Swint-Kruse has classified it as a gain-of-function syndrome. |
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Term
Lysosomal Storage Diseases (general) |
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Definition
I cell disease, Gaucher's disease, Tay-Sachs Disease, Hurler's Syndrome - Lysosomal storage disease occur if any of the lysosomal enzymes are defective or absent.
- Digestion of the products stop at the stage of the missing enzyme and cannot be processed further. Because of incomplete digestion, there are no transporters that recognize the product so it builds up inside the lysosome.
- If the lysosome is not expelled by the tissue (neurons can’t) they burst and the buildup of debris causes problems.
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Term
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Definition
| essentially resulting from generalized undernourishment, marasmus-like protein-energy malnutrition has a very long course (months to years) and will result in severely low body fat, mild hypoalbuminemia, loose skin, and starvation. Patients do not experience edema, as they are overall energy deficient (and not suffering a protein imbalance) |
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Term
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Definition
| Marfan's syndrome is a disease characterized by the lack of fibrilin-1 within the body. This results in a lack of elastin as well. Patients with Marfan's are often tall, with extended chests, long digits and extremities, mitral valve prolapse, and aortic root dilation and aortic dissection.Connective Tissue 08.14.2008 In Marfan's Syndrome, fibrillan-1 is unable to store TGF-β, allowing TGF to run amok and over-produce growth in a variety of cellular functions: proliferation, differentiation, etc - this is due to a deletion at the primary structure level. |
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Term
Medium-Chain Acyl-CoA Dehydrogenase (MCAD) Deficiency |
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Definition
| without MCAD, fatty acid oxidation does not occur beyond the long-chain species, which leads to impaired metabolism of medium-length fatty acids. During fasting and after glycogen has been consumed, the body is unable to process the medium-length fatty acids. This can be diagnosed by a blood spot with mass spec and managed with a controlled diet |
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Term
Muscular Dystrophy (general) |
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Definition
| mutations in dystrophin or other proteins linking muscles to the plasma membrane result in dystrophies |
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Term
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Definition
| kidney: faconi syndrome; heart: cardiomyopathy, conduction blocks, failure; liver: failure (especially in infants); Skeletal muscle: weakness, cramps, exercise intolerance; Pancreas: diabetes; eyes: drooping eyelids, inability to move eyes laterally, blindness; Nervous tissue: stroke before 40, dementia, developmental delay, tremors, seizures, poor balance |
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Term
| Neurodegenerative diseases (general) |
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Definition
| the result of defects in kinesin-mediated long distance transport along microtubules |
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Term
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Definition
| Auto-antibodies are produced to specific desmoglein 1, causing desmosomes to lose their connection to keratin, resulting in blistering and crusty sores. Pemphigus foliaceus is not seen in the oral cavities |
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Term
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Definition
| Dr. McGregor's sister experienced this: autoantibodies are generated for desmoglein 3, affecting desmosomes and causing blistering of the body and oral cavities |
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Term
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Definition
| related to laminopathies, progeria is a disease involving rapid aging |
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Term
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Definition
| is the most common form of a group of progressive neurodegenerative disorders characterized by the clinical features of parkinsonism, including bradykinesia (a paucity and slowness of movement), rest tremor, muscular rigidity, shuffling gait, and flexed posture. Nearly all forms of parkinsonism result from a reduction of dopaminergic transmission within the basal ganglia. Lewy body dementia, abnormal round structures — called Lewy bodies — develop in regions of your brain involved in thinking and movement. Gross examination of the brain in PD reveals mild frontal atrophy with loss of the normal dark melanin pigment of the midbrain. Microscopically there is degeneration of the dopaminergic cells with the presence of Lewy bodies (LBs) in the remaining neurons. LBs have a high concentration of –synuclein and mutations in the synnuclein gene can cause familial PD. |
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Term
| Polycystic Kidney Disease |
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Definition
| defects in the kinesin complexes that carry cargo to the apical region of cilia/flagella result in polycystic kidney disease |
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Term
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Definition
| deficiency in lysosomal α1-4 and α1-6 glucosidase results in the accumulation of glycogen in the lysosomes. |
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Term
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Definition
| a peroxisomal disorder, likely due to an issue with transport. Patients with Refsum's Disease present with neurologic damage, cerebellar degeneration, and peripheral neuropathy. Onset is most commonly in childhood/adolescence with a progressive course, although periods of stagnation/remission occur. Symptoms also include night blindness, ataxia, scaly skin (ichthyosis), difficulty hearing, and eye problems including cataracts |
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Term
Rhizomelic chrondrodysplasia punctata |
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Definition
| Rhizomelic chondrodysplasia punctata is caused by peroxisomes being unable to synthesize plasmalogens, which leads to defective myelinization of neurons, causing severe neurologic disease and defects in the skeleton during development. |
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Term
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Definition
| resulting in either a single or double inherited mutation, patients will experience a sickling of red blood cells when deoxygenated of varying degree, dependent on the number of mutations. These cells are more likely to adhere to one another in addition to the walls of the vasculature. Sickled cells are not able to pass through capillaries as easily as normal rbc's and are especially prone to occlude blood flow in the spleen and capillary beds of the extremities |
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Term
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Definition
| Intestinal SGLT1: glucose/galactose malabsorption leads to severe diarrhea (fructose utilized as a dietary alternative); Familial Renal Glucosuria by Kidney SGLT2: large amounts of glucose are excreted |
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Term
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Definition
| Tay-Sachs occurs when gangliosides are permitted to accumulate in the brain due to a decrease in the amount or effectiveness of lysosomes in nervous tissue to break down β-hexosaminidase |
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Term
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Definition
| loss of a hemoglobin subunit, which will result in a decrease or loss of function. There are several variants of thalassemias. |
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Term
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Definition
| deficiency in Glucose-6-phosphatase causes G-6-P to accumulate in the liver and renal tubules, resulting in hypoglycemia and lactic acidemia |
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Term
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Definition
| a lack of peroxisomes that is likely due to an error in transport. Zellweger's is associated with a lack of PEX 1,2,3,5,6,12,14, and 26. Patients exhibit liver disease, hypotonia, neonatal seizures, cataracts, retinopathy, renal cysts, and other complications |
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Term
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Definition
| an auto-hemolytic anemia- molecular defect in one or more of the proteins (spectrin, ankyrin) of the red blood cell cytoskeleton. This causes leaky sodium transport, and a decreased membrane to cell volume ratio- causing the sphere shape. They get trapped in the spleen which lysis them causing anemia. |
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Term
| Dehydrated hereditary stomatocytosis |
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Definition
| mutation in ion channel, hemolysis is accomapanied by increase reticulocytes. |
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Term
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Definition
| red blood cells are elliptical. Mutation in spectrin. Diminished levels of band 4.1 protein leads to anemia. |
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Term
| Amytrophic lateral sclerosis (ALS) |
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Definition
(Lou Gehrig's Disease) a progressive, usually fatal, neurodegenerative disease caused by the degeneration of motor neurons, the nerve cells in the central nervous system that control voluntary muscle movement. |
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Term
| Charcot-Marie Tooth disorder type II |
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Definition
| progressive peripheral neuropathy, similar to that caused by diabetes. Later in life than type 1. Caused by lamin A-mutation. |
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Term
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Definition
cobalamin deficiencies have been linked to pernicious anemia (primarily due to poor secretion of a stomach protein necessary for B12 absorption) ,megaloblastic anemia* (also folate deficiency), and neuropathies. |
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Term
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Definition
In Down's Syndrome, there are 3 copies of many genes, causing many proteins to be up-regulated and one to be down-regulated - a failure of protein expression |
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Term
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Definition
a diet high in pumpkin, carrot, and orange juice can lead to an orangish pigmentation of the skin, much like what is seen in jaundice. Patients with hypercarotinemia will have normal eye coloring and biliruben levels, allowing a differentiation from a jaundiced patient. |
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Term
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Definition
insufficient amounts of folate can result in neural tube defects (during development), homocyteinemia, and megaloblastic anemia* |
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Term
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Definition
a deficiency in cobalamin and/or folate will lead to megaloblastic anemia, a bone marrow disorder affecting erythroid, myeloid, and/or platelet generation. Myelotoxic drugs and certain retroviruses can have a similar effect on the bone marrow. In folate deficiency, the folate concentration will be low in the serum and erythrocytes. This causes the cells to remain stuck in S phase, causing hemoglobin concentration to be low, while homocysteine concentration in the serum will be increased. RBC's will become macro-ovalocytic (larger and oval-shaped) |
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Term
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Definition
A high concentration of cholesterol, saturated and trans-unsaturated fatty acids, and antioxidants will contribute to artherosclerosis. A deficiency of pyridoxine, folate, and B12 will lead to homocysteinemia (too much homocysteine). High sodium results in hypertension, and a lack of calcium and/or vitamin D will contribute to osteoporosis. |
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Term
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Definition
Resulting from a lack of vitamin D and/or Calcium, patients with Ricket's will demonstrate large wrists, bowed long bones (such as the femur), rachitic rosary (The knobs of bone at the costochondral joints of patients appear as large beads under the skin of the rib cage, resembling rosary beads)Wikipedia, cranial deformities, and delayed tooth development |
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Term
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Definition
| caused by Vitamin B12 deficiency. Accumulation of this F.A. in neurons causes peripheral neuropathy. |
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