Term
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Definition
| This condition is caused by ascorbic acid (vitamin C) deficiency. Vitamin C is essential for the synthesis of collagen and is a cofactor of prolyl- and lysyl hydroxylases (enzymes that catalyze the formation of hydroxyprolines and hydroxylysine). With this condition, wounds do not heal well and blood vessels become fragile. Patients are literally "melting": insufficient hydroxylation of collagen results in less thermostable collagens and the melting temperature of collagens is reduced below 37 degrees celcius. Therefore, collagens cannot maintain their helical structure at body temperature. |
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Definition
| This disease is caused by accumulation of the amyloid plaque amayloid β, a peptide containing 40-42 amino acid residues. This peptide, when aggregated in a β-pleated sheet configuration, is neurotoxic. Another factor involved in the development of this disease is the accumulation of neurofibrillary tangles in the brain. A key component of these tangled fibers is an abnormal form of the tau protein, which in its healthy version helps in the assembly of the microtubular structure. The defective tau protein appears to block the actions of its normal counterpart. |
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Term
| Creutzfeldt-Jakob Disease (humans), Scrapie (sheep), and Bovine Spongiform Encephalopathy ("mad cow disease," cattle) |
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Definition
| These transmissible spongiform encephalopathies are caused by an infectious prion protein (PrP). The infectious PrP has the same amino acid and gene sequences as the noninfectious form, but is an altered version of the normal protein in that a number of α-helices present in noninfectious PrP are replaced by β-sheets in the infectious form. This conformational difference confers relative resistance to proteolytic degradation of infectious prions and permits the accumulation of insoluble fibrils. The infectious PrPs act as "templates" for converting the normal PrP to the pathogenic conformation. These diseases are fatal and there is currently no treatment to alter this outcome. |
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Term
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Definition
| This disease is characterized by deformed bones, joint dislocations, and aortic aneurysms. It is caused by defective collagen cross-linking due to inhibition of lysyl oxidase by a plant toxin, β-aminopropionitrile, present in sweet peas and other Lathyrus species. |
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Term
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Definition
| Causes symptoms similar to Lathyrism (deformed bones, joint dislocations, aortic aneurysms) because lysyl oxidase (an enzyme that participates in the formation of covalent cross-links in collagen) is a copper-requiring enzyme. |
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Term
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Definition
| A G-->T mutation in the base 3615 of human pro-α1 (I) collagen results in a lethal form (type II) of this disease. With this disease, there is a characteristic facial appearance and marked proximal shortening of the limbs. Additionally, the long bones appear "crumpled." In the non-lethal type II form of this disease (inherited), the patient may have bone malformation, joint dislocations, and blue sclera. |
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Term
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Definition
| This syndrome is caused by degradation or accumulation of defective collagen in the intracellular compartments due to errors in the processing of type I, III, or V procollagens--that is, a mutation prevents posttranslational processing of collagen. The symptoms of this syndrome include large joint hypermobility, cigarette-paper scars and heme pigment accumulation, small joint hypermobility, and skin hyperextensibility. |
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Term
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Definition
| This condition results from the destruction of the connective tissue of alveolar walls (lung tissue cannot regenerate). In the normal lung, the alveoli are chronically exposed to low levels of neutrophil elastase (an enzyme that degrades elastin) released from activated and degenerating neutrophils. In α1-Antitrypsin deficiency (α1-AT is a serine protease inhibitor that inhibits elastase), this proteolytic activity can destroy the elastin in alveolar walls. Smokers are particularly prone to this disease because they are constantly breathing in foreign particles, stimulating neutrophil activity and the subsequent release of elastase. |
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Term
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Definition
| These include certain muscular dystrophies (e.g. Emery-Dreifuss muscular dystrophy), cardiomyopathy, partial lipodystrophy, and progeroid syndromes (e.g. Hutchinson-Gilford progeria syndrome, a disease where children age very rapidly and die at a young age) and are caused by mutations in genes encoding for the lamins, the major protein constituents of the nuclear lamina. |
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Term
| Limb girdle muscular dystrophy 2B |
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Definition
| A progressive muscle degeneration caused by a mutated form of the protein dysferlin. Dysferlin is a membrane protein that is thought to function in membrane repair to "patch" holes that can form in the plasma membrane of skeletal muscle fibers. Thus defective membrane repair can lead to muscle degeneration. |
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Term
| Chronic Granulomatous Disease |
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Definition
| An inherited condition in which leukocytes have non-functional NADPH oxidase and cannot kill phagocytosed microbes efficiently. Patients with this disease suffer from chronic infections and a shortened life expectancy. |
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Term
| Neimann-Pick Disease, Tay-Sachs Disease, Hurler's Disease |
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Definition
| These are examples of lysosomal storage diseases. This class of disease was among the first genetic diseases to be recognized and result from an accumulation of material in lysosomes. Generally these diseases result from non-functional lysosomal enzymes. Thus, mutations in a single gene that leads to a non-functional (or absent) lysosomal enzyme results in the accumulation of the substrate for that enzyme in the lysosome. These diseases are generally severe in nature. |
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Term
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Definition
| A peroxisomal disease that results in childhood death. This condition is due to the failure of importation of multiple peroxisomal enzymes across the peroxisomal membrane. |
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Term
| Neonatal Adrenoleukodystrophy |
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Definition
| One of approximately 50 peroxisomal diseases. |
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Term
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Definition
| A structural abnormality involving the absence of dynein arms in cilia and flagella. Ciliary motility is impaired and there is reduced or no ciliary transport of mucus in the tracheobronchial system leading to chronic respiratory difficulty. Visceral asymmetry may also be associated with this condition. Males with this syndrome are sterile since the flagellum of the sperm is immotile. |
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Term
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Definition
| Can be caused by early activation of pancreatic zymogens (proenzymes) |
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Term
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Definition
An X-linked recessive deficiency in the enzyme glucose-6 phosphate dehydrogenase in the monophosphate shunt, especially in RBCs. Glucose-6-phosphate dehydrogenase converts glucose-6-phosphate into 6-phosphate-gluconate which is then converted into ribulose-5-phosphate. Both of these reactions generate NADPH needed to maintain glutathione (part of the enzyme glutathione peroxidase, the major intracellular ROS detoxification system) in its reduced form (GSH).
Oxidative stress in these patients, often in the form of infection treated with a sulfonamide containing antibiotic, induces a hemolytic anemia in those RBCs that are deficient in G6PD characterized by aggregation of hemoglobin (Heinz bodies) in RBCs. Eating fava beans, taking aspirin, antimalarial primaquine, or any other drug that is either an oxidant itself or produces oxidizing products during its metabolism can also cause this oxidative stress. |
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Term
| Pyruvate kinase deficiency |
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Definition
| The most prevalent disorder of glycolysis; genetic deficiency of this enzyme in erythrocytes can result in hemolytic anemia (excessive erythrocyte destruction) that can be treated with folic acid supplementation. |
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Term
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Definition
| Occurs in people with excessive fructose in their diets--the excessive fructose in the diet causes an accumulation of Fructose-1-Phosphate and sequestering of inorganic phosphate in the cells, which limits the rate of production of ATP from ADP and inorganic phosphate, especially in the liver which metabolizes most dietary fructose. This is because the conversion of fructose to fructose-1-phosphate by fructokinase is rapid, but the conversion of fructose-1-phosphate by aldolase B to dihydrozyacetone phosphate and glyceraldehyde is slow. The excess of ADP is then catabolized to AMP and to uric acid. |
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Term
| Hereditary fructose intolerance (fructose poisoning) |
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Definition
| Caused by a deficiency in Aldolase B, the enzyme that cleaves fructose-1-phosphate. This defect leads to trapping of fructose-1-phosphate that allosterically inhibits glycogen phosphorylase, resulting in severe hypoglycemia. It also causes vomiting, jaundice, hemorrhage, and eventually hepatic failure. Treatment is rapid detection and avoidance of fructose and sucrose in the diet. |
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Term
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Definition
| A benign condition caused by a deficiency in fructokinase. |
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Term
| Hereditary fructose intolerance due to fructose 1,6-bisphosphatase deficiency |
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Definition
| Results in fructose-induced hypoglycemia despite the presence of high glycogen reserves, because fructose 1,6 bisphosphate that accumulates in the absence of bisphosphatase allosterically inhibits glycogen phosphorylase in the liver. |
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Term
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Definition
| Results from deficiency of the enzyme uridylyltransferase, resulting in accumulation of galactose-1-phosphate and galactose. The excess galactose is converted to galactitol and the physiological consequences are similar to those observed in excess fructose intake and in essential fructosuria with the exception that a wider spectrum of tissues is affected. Therapy for this autosomal recessive disorder is rapid diagnosis and elimination of lactose from the diet. |
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Term
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Definition
| The enzyme galactokinase is missing, leading to the accumulation of galactose. When galactose levels are high, the enzyme aldose reductase (present in liver, lens, nerve tissue, seminal vesicles) converts it to galactitol. Elevated levels of galactitol can cause cataracts. |
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Term
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Definition
| There are three types: congenital or transient deficiency in premature infants, deficiency secondary to the surgical removal of the small intesting, and deficiency caused by mucosal cell damage. The enzyme β-galactosidase that converts lactose to galactose is deficient in these individuals. |
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Term
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Definition
| Type I glycogen storage disease caused by a defect in the glucose-6-phosphatase enzyme (enzyme responsible for converting glucose-6-phosphate back to glucose). This disease affects the liver and kidney because of the increased amount of glycogen in these tissues. It is characterized by a massive enlargement of the liver (probably due to immediate conversion of G-6-P into glycogen), severe hypoglycemia (free glucose not being formed), and an inability to process lactose normally. Can be fatal. |
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Term
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Definition
| Type II glycogen storage disease caused by a defective α-1,4-Glucosidase (lysosomal) enzyme. The disease affects all organs due to a massive increase in glycogen and is associated with cardiorespiratory failures, death (usually before age 2), and accumulation of glycogen in lysosomes. |
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Term
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Definition
| Type III glycogen storage disease caused by a defective amylo-1,6-glucosidase enzyme (debranching enzyme). This disease affects muscle and liver because of increased accumulation of glycogen. The clinical features of the disease are similar to those of type I, but are milder in course (include hepatomegaly, hypoglycemia, and inability to process lactose normally). |
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Term
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Definition
| Type IV glycogen storage disease caused by a defective branching enzyme (α-1,4->α-1,6) from glycogen synthesis. The liver and spleen are affected and abnormal, unbranched glycogen is formed. This disease causes progressive cirrhosis of the liver and liver failure causes death, usually before age 2. |
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Term
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Definition
| Type V glycogen storage disease caused by defective glycogen phosphorylase, an enzyme involved in glycogen breakdown. This disease affects muscle tissue and leads to a moderately increased amount of glycogen. Its primary symptom is painful muscle cramps and, other than this, the patient is normal. (There is no obvious known biochemical explanation for why accumulation of glycogen causes muscle cramping.) |
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Term
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Definition
| Insulin-dependent; represents 10% or fewer of all cases and is caused by inadequate secretion of insulin by β-islets of Langerhans in the pancreas, generally the result of autoimmune destruction of the islets. Usually begins earlier in life and most patients are thin, have elevated levels of blood glucose, and elevated levels of ketones. The treatment is straightforward: administer insulin. |
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Term
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Definition
| This type of the disease is non-insulin dependent, arises later in life, and represents 90% of all cases. Patients are generally obese and insulin release is accelerated in response to overeating. Excess insulin results in insulin resistance, due to lack of insulin receptors or insensitivity to insulin of the receptors. The high glucagon/functional insulin ratio in diabetes promotes glycogen breakdown. When the glucose concentration in the blood exceeds the reabsorption capacity of the renal tubules, it is excreted in the urine. Fortunately, weight reduction by most patients can correct the metabolic derangements. |
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Term
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Definition
Caused by the inactivation of 1-4 copies of the α-globin gene usually due to deletions.
If one copy is inactive, this person is a "silent carrier" and will not show symptoms.
If two copies are inactive, patient is said to have the α-thalassemia trait or α-thalassemia 1. He will have a reduced mean cell volume, but be relatively asymptomatic.
If three copies are inactive, patient has the hemoglobin H disease, detectable levels of β4 tetramers due to the predominance of β chains, and moderate to marked anemia present at birth. This condition is not lethal.
If four copies are inactive, tetramers of γ chains (known as hemoglobin Bart's) is the predominant fetal hemoglobin. γ4 has virtually no oxygen-carrying capacity and the patient will have profound anemia, heart failure from the unoxygenated heart attempting to pump a small amount of dissolved oxygen in blood to oxygen-starved tissues, marked edema (hydrops fetalis), and there will be stillbirth or neonatal death. |
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Term
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Definition
| Results from mutations in the β-globin gene; autosomal recessive; usually due to a variety of sometimes subtle mutations (over 100 different mutations cause this disease); variety of mutations result in clinical heterogeneity from minor to major (transfusion dependent) anemia |
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Term
| Heinz body hemolytic anemias |
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Definition
| Due to several different point mutations usually in the hydrophobic center (usually in the β-subunit) that result in an unstable hemoglobin molecule that coagulates (heinz body) in the erythrocyte |
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Term
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Definition
| Mutation from glutamate to valine at position 6 of the β-subunits (βglu6-val); autosomal recessive; switch from hydrophilic to hydrophobic residues makes the protein "sticky" particularly in the T-state and prone to polymerization. |
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Term
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Definition
| Caused by an accumulation of cholesterol in cells. Characterized by yellow masses on the heels and knees and may be indicative of hypercholesterolemia. |
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Term
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Definition
| Build up of cholesterol on vessel walls; on histological examination, "crystals" of cholesterol seen. Also associated with dystrophic calcification. |
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Term
| α1-Anti-trypsin Deficiency |
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Definition
| An autosomal recessive disease that causes abnormal protein folding. Because of the inability to inactivate PMN proteases, A1AT accumulates in the endoplasmic reticulum of hepatocytes as red (eosinophilic) globules. |
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Term
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Definition
| Disease caused by protein malformation/poor protein folding. |
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Term
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Definition
| Accumulation of carbon pigment in the lung. Also known as "black lung." Common in coal miners. Causes scarring of the lung. |
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Term
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Definition
| Carbon deposition in lungs, not particularly harmful; can occur from smoking, living in an urban area. |
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Term
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Definition
| A group of systemic and localized diseases. Related to chronic inflammation, cancer, or gene mutation. Characterized by extracellular deposition of a fibrillar protein (B-pleated sheet, stain w/ congo red stain), enlarged glenohumeral joint, sawtooth appearance of tongue, and abnormal pigmentation or growths around eyes (last three symptoms of the disease if left untreated). |
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