Term
21-Hydroxylase Deficiency
Steroid Hormone Synthesis |
|
Definition
| 21-hydroxylase deficiency (required for synthesis of glucocorticoids and mineralcorticoids) leads to increased secretion of ACTH by anterior pituitary (lack of feedback inhibition). This causes enlarged adrenals (hyperplasia) w/ accumulation of pregnenolone, progesterone, and androgens. symptoms include early virilization, short stature (early bone maturation). loss of Na in urine. Hypotension, possible shock or sudden death. Can be treated by hormone replacement. |
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Term
Acreuloplasminemia
ceruloplasmin |
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Definition
| The absence of ceruloplasmin (a copper feroxidase the facilitates iron release from cells) leads to accumulation of iron in the spleen, heart, liver, kidney, thyroid and retina (damage). Diabetes mellitus to destruction of the beta cells of the pancreas. |
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Term
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Definition
| can be caused by conditions (s/a thalassemia or sideroblastic anemia) that require transfusions. These conditions themselves contribute minimally to the iron-loading, but the transfusion is the major factor. Can also be caused by chronic liver disease (alcoholism), Porphyria Cutanea Tarda (responds to phlebotomy - patients are commonly heterozygotes for the HFE mutation), dietary ingestion (bantu beer), etc. EPO production is down regulated, decreasing formation of RBC from bone marrow. |
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Term
Acquired Poryphyrias
Heme Synthetic Pathway |
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Definition
| In porphyrias, there is a disruption in the heme synthetic pathway. Acquired porphyrias can be the result of exposure to various agents (e.g., alcoholism, pesticides, herbicides, tumors, iron overload). |
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Term
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Definition
| If there is an excess of GH in adults, excessive remodeling leads to thickening of bones - especially facial bones by the eyebrows and enlargement of hands and feet. |
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Term
Acute Myocardial Infarction
Troponin Isozymes |
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Definition
| Troponin isozymes TnT and TnI are elevated in acute MIs and are used as markers for cardiac muscle damage. |
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Term
Alkaptonuria
Homogentistate Oxidase |
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Definition
| Leads to the accumulation of homogenitisic acid in urine, which turns black on reaction of O2. accumulation of polymerized forms results in arthritis, calcification in the cardiovascular system and urinary tract, and a reddish tint to the skin. |
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Term
Alzheimer's
Late Onset in 75% |
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Definition
| deposition of two fibrillary proteins: beta-amyloid (amyloid plaques) and Tau protein (neurofibrillary tangles). susceptibility gene (Apo E) at 19q13 and a different susceptibility gene locus on chromo. 12q. Multifactorial. |
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Term
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Definition
| amniotic rupture leads to exposed chorion then transient oliohydramnios and fetal constraint. Disruption by amniotic bands. |
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Term
Anaphylactic Shock
Mast Cells, basophils |
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Definition
| An intense generalized response following a second exposure the same allergen. A large number of basophils and mast cells degranulate, leading to widespread vasodilatation and increased permeability. This leads to reduction of blood volume (as well as constriction of the bronchioles - respiratory insufficiency) and sends the person into circulatory shock. |
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Term
| Anemia of Chronic Disease |
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Definition
| A cytokine-mediated anemia seen with infections, inflammation, cancer. Cytokines act on the liver, increasing hepsidin production causing the iron to be trapped in cells (enterocytes, hepatocytes, macrophages) and less to be absorbed from the diet. Decreased iron-transferrin in serum. unlike iron deficiency, the transferrin levels either remain the same of decrease (no increase in iron binding capacity). marrow doesn't compensate with increased RBC production. |
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Term
Angelman Syndrome
UBE3A Gene |
|
Definition
| Severe MR, hypotonia of trunk and hypertonia of extremities. Absent speech. Movement or balance disorder. Seizures. Protruding tongue, hypopigmentation. Maternal del(15q11q13) or imprinting center mutation. Few uniparental disomy (UPD) - paternal. UBE3A gene product transfers ubiquitin; imprinting restricted to brain. |
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Term
| Anhidrotic Ectodermal Dysplasia |
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Definition
| Caused by a mutation of an X chromosome gene resulting in a lack of sweat glands. Occurs in patches reflecting the mosaicity of X chromosome inactivation. |
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Term
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Definition
| mutation of PAX6 - dominant type 2 aniridia (no iris or very rudimentary iris). Blindness, glaucoma. |
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Term
Acquired Hemolytic Anemia
PIGA Enzyme, GPI Anchors |
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Definition
| the PIGA enzyme is essential for GPI anchor synthesis. GPI (glycosylphosphatidylinositiol) is used to anchor proteins to the membrane. When PIGA is mutated, the GPI anchors are not attached. One impacted protein, CD59, normally inhibits C3 convertase in the alternate complement pathway. Without CD59 at the membrane, the cells are more sensitive to complement-mediated lysis, leading to thrombosis. |
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Term
Arginase Deficiency
Urea Cycle |
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Definition
| Deficiency leads to elevated arginine and ammonia in the plasma, CSF, and urine; arginine, lysine, and ornithine elevated in urine. Treated with a arginine-free, low protein diet. |
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Term
Arginosuccinase Deficiency
Urea Cycle |
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Definition
| deficiency leads to elevated argininosuccinate and ammonia levels in plasma, CSF and urine. Recessive - usually fatal in first two years. Treated with arginine. |
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Term
Argininosuccinate synthetase deficiency
Urea Cycle |
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Definition
| Deficiency leads to elevated citrulline and ammonia levels in the plasma, CSF and urine. Recessive. Treated with arginine - enhances citrulline excretion. |
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Term
arginosuccinic aciduria
arginosuccinic acid lyase |
|
Definition
| acute ataxia, lethargy, patchy alopecia and skin changes (abnormal collagen), intention tremor. Increased plasma ammonia (underlying problem). Use sodium benzoate and sodium phenylbutyrate for episodes of hyerammonimia. Supplement diet w/arginine, restrict dietary protein. |
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Term
atherosclerosis
Cholesterol |
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Definition
| Cholesterol in carried by LDL in the blood. Oxidized LDL is taken up by macrophages, which enlarge to become "foam cells". Foam cells are trapped in BV walls, leading to the formation of cholesterol-rich plaque. As lumen is narrowed by plaque, blood flow is restricted. |
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Term
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Definition
| initiation: endothelial injury due to: smoking, diabetes, hypertension, genetic abnormalities, insulin resistance ischemia, peripheral artery disease, inflammation, obesity, dyslipidemia, hyperhomocysteinemia. Once the endothelium in injured, LDL-C can enter (smaller LDLs are worse) and they become oxidized. Once oxidized, they attract monocytes and promote the production of CAMs, allowing more LDLs and macrophages to be present. oxLDL is picked up by macrophages by attaching to the scavenger receptor (no feedback inhibition). hypertrophy and form foam cells. activated smooth muscle cells move in (pro-inflammatory). endothelial cap stability is an important factor in plaque stability. |
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Term
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Definition
| thiamine deficiency - currently a problem with alcoholic malnutrition. Supplemented in flour. |
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Term
beriberi (dry)
pyruvate dehydrogenate complex |
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Definition
| a chronic minor deficiency in thiamine, leading to disturbances in carbohydrate metabolism and decreased transketolase activity. Symptoms include peripheral neuropathy, fatigue, and impaired capacity to work. also impacts the alpha-KGDC (and other thiamine dependant enzymes), but PDC is gatekeeper. |
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Term
beriberi (wet)
pyruvate dehydrogenate complex |
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Definition
| a severe thiamine deficiency leads to neurologic manifestations, cardiovascular symptoms (more apparent) s/a heart enlargement and tachycardia. Cardiac failure is common after stress, and edema and anorexia are characteristic. |
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Term
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Definition
| Rare - unless antibiotics of the ingestion of v. large amounts of avidin (present in raw egg whites). |
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Term
Blooms Syndrome
BLM helicase |
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Definition
| Recessive mutation in BLM helicase- accelerated aging. Cardiovascular disease, arthritis, cancer. Chromosomal and genomic instability. |
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Term
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Definition
| loss-of-function mutation of SOX9 results in underdeveloped throrax, bent limbs, and sex reversal (XY female) |
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Term
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Definition
| The mutation of the Ras protein causes it to be unable to hydrolyze bound GTP. The Ras signal is constitutively on and activates downstream protein kinase cascades that promote cell growth. |
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Term
Carnitine Palmityltransferase (acyltransferase) Deficiencies
fatty acid catabolism |
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Definition
| Autosomal recessive deficiency in CPTI or CPTII - can't transfer long chain fatty acids into mitochondria. Symptoms are triggered by exercise or fasting, and can be treated with a high carb, low-fat diet and short or medium chain triglycerides (don't need a carrier - can diffuse) |
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Term
|
Definition
| CDKIs (CDK Inhibitors), such as p16 mutations, are involved in the development of multiple tumor types, including: head and neck, pancreatic, non-small-cell lung carcinoma. |
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Term
|
Definition
| Cholera toxin causes the irreversible covalent modification of the alpha-subunit of Gs (attaches an ADP-ribose group to an arg residue), locking it in the GTP-bound state. The causes the constitutive activation of adenylate cyclase giving high levels on cAMP. This causes persistent activation of PKA, which phosphorylates a chloride channel - leads to excessive loss of NaCl and water in the intestine. |
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Term
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Definition
| CO binds reversibly to the O2 site, but with a much greater (200x) affinity. O2 has a higher affinity for CO ligated Hb, but cannot be effieciently released from it in peripheral tissues. |
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Term
Collagen disease
collagen fibers |
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Definition
| elevated levels of glycine in the urine are indicative of collagen disease |
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Term
colorectal cancer
cyclin D2 |
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Definition
| Cyclin D2 has been shown to be amplified in colorectal cancer |
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Term
complete androgen insensitivity syndrome
androgen receptor |
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Definition
| XY females with testicular tissue that secretes androgents, but there is an androgen receptor defect. Phenotypically normal females - sparse axillary and pubic hair, short vagina, remnants of uterus and fallopian tubes. |
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Term
congenital adrenal hyperplasia
21-hydroxylase |
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Definition
| 21-hydroxylase deficiency (others possible but this is most common) results in overproduction of androgens and virilizaiton female infants. Internal structures normal. |
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Term
| Contiguous Gene Syndromes |
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Definition
| common features: microduplications or microdeletions - require FISH to visualize. Phenotype tends to be variable due to different breakpoints. Occurrence is usually sporadic, but may cluster in families. |
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Term
|
Definition
| premature fusion of the sutures (some). Can cause Crouzon or Apert syndrome. |
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Term
Cri du Chat Syndrome AKA 5p Minus
chromosome 5 |
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Definition
| chromosome 5p deletion. Infant's cry sounds like a cat. |
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Term
Crigler-Najjar syndrome
UDP-glucuronosyl transferase |
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Definition
| rare recessive disorder that results in moderate (type II) to severe (type I) jaundice due to reduced or absent UDP-glucuronosyl transferase activity (rate limiting enzyme). Type II often responds to inducers (Phenobarbital) of the enzyme while type I may require liver transplantation. caused by a number of different mutations. Kernicterus seen in type I. |
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Term
Cystic Fibrosis
chloride channel gene (7q31) |
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Definition
| Mutations in CFTR (cystic fibrosis transmembrane regulator gene), located on 7q31, cause reduced or absent activity of the chloride channel. 3 bp deletion at codon 508 accounts for 70% of mutations. Autosomal recessive. 1/25 carrier frequency. Causes pulmonary disease, meconium ileus (10-20% of newborns), pancreatic insufficiency, and male infertility. |
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Term
Cystic Fibrosis
ABC-type chloride channel |
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Definition
| most commonly due to the expression of a mutant protein, deltaF508 CFTR. In this protein, the ABC-type Chloride channel is made (primary active transporter) but has a single AA deletion. Consequently, it doesn't make it to the membrane and chloride builds up in the cell, drawing in water. This dehydration leads to thick mucus and defective function of the respiratory tract cilia, as well as increased infections. |
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Term
Cystinosis
cysteine transport |
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Definition
| results from a defect in cysteine transport, causing a deposition of cysteine crystals in tissues - mortality from renal failure. |
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Term
Cystinuria
kidney transporter |
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Definition
| a defect in the kidney transporter involved in the reabsorption of some amino acids leads to the excretion of cystine, lysine, arginine, and ornithine. Cystine (least soluable) forms calculi in kidney tubules. |
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Term
Deficiency of vitamin A
epiphyseal plate |
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Definition
| If there is a deficiency of vitamin A in a growing child, there will be a decrease in the growth rate, leading to a lack of bone resorption during remodeling. Bone growth won't keep up with the rest of the body and the cranial cavity and spinal column won't enlarge fast enough. |
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Term
|
Definition
| occasionally associated with mtDNA deletions or duplication sin certain pedigrees showing a maternal pattern of inheritance. |
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Term
DiGeorge Syndrome/Velocardiofacial Syndrome
22q11.2 |
|
Definition
| a developmental field defect caused by a chromosome 22q11.2 microdeletion. Cleft palate. parathyroid hypoplasia, thymus hypoplasia, immunodeficiency, cardiac defects, renal and urinary tract defects, mental retardation. |
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Term
|
Definition
| eEF-2 normally mediates the traslocation of a developing polypeptide with the hydrolysis of GTP. Diphtheria toxin catalyzes the ADP-ribosylation of eEF-2, which inactivates it. |
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Term
disorders of laterality
ZIC3 |
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Definition
| ZIC3 mutations lead to disorders of laterality - Situs inversus (everything flipped) or Situs ambiguus (no specifice symmetry) |
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Term
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Definition
| Trisomy 21. Mental retardation. Flat nose, close-set eyes. Slanting eyelids, protruding tongue. Hypotonia; predisposition to leukemia. Amyloid precurser protein (APP) on chromo. 21 - will develop alzheimer's-like disease. 1/800. 85% maternally derived. |
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Term
Duchenne Muscular Dystrophy
dystrophin (an actin assoc. ptn. Found in muscle cortical networks) |
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Definition
| a genetic defect causes dystrophin to be dysfunctional or absent. Dystrophin cross-links the actin filaments into a supportive network and also functions to connect the internal cytoskeleton to the external matrix. As a result, the muscle cell is easily damaged and the disease is ultimately fatal. |
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Term
|
Definition
| Trisomy 18. flaccid, clenched fists (overlapping fingers). Rocker-bottom feet. Renal malformations, congenital heart defects. 1/8000 |
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Term
Ehlers-Danlos syndrome (type unknown)
collagen fibers |
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Definition
| a defect in lysyl oxidase results in hyperextensible skin and joints. Lysyl Oxidase covalently links hydroxylysine residues in adjacent tropocollagen molecules, creating insoluble fibrils. It also covalently links tropoelastin molecules to form elastin. |
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Term
Ehlers-Danlos, Type IV
Collagen type III |
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Definition
| Deficiency in type III collagen makes aneurysms and intestinal rupture common. |
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Term
Ehlers-Danlos, Type VII
collagen fibers |
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Definition
| Procollagen Peptidase can no longer cleave procollagen, causing poor aggregation and binding of the procollagen molecules into fibers. This leaves the fibers weak, giving the patient hyperflexible joints, dislocations, and soft skin. |
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Term
Emphysema
elastic fiber of lungs |
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Definition
| the breakdown of the elastic fibers in the alveoli of the lungs leads to a loss of lung elasticity. This means that air in not forced out of the lungs, and the patient becomes barrel-chested and their tidal volume decreases. The elastic fibers are degraded by elastase, which is normally kept in check by alpha1-antitrypsin (which is inhibited by cigarette smoke, among other things). |
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Term
esophageal, breast, and gastric cancers
cyclin D1 |
|
Definition
| an over-expression of cyclin D1 is associated with these cancers |
|
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Term
essential fatty acid deficiency
fatty acid synthesis |
|
Definition
| infants do not get essential fatty acids (s/a linoleic and linolenic acids that can not be manufactured by the body), causing decreased growth, skin abnormalities, impaired immune response. Remedy - supplement EFA |
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Term
ethanol inhibition of gluconeogenesis
gluconeogenesis |
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Definition
| the metabolism of ethanol requires NAD+ and doesn't regenerate it. This can inhibit gluconeogenesis, leading to hypoglycemia and lactic acidosis. |
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Term
|
Definition
| > 15 mg: increased lung cancer and mortality in smokers |
|
|
Term
|
Definition
| >1 mg: can mask anemia due to vitamin B12 deficiency |
|
|
Term
|
Definition
| >500 mg: monitor for liver toxicity. Can lead to fulminant hepatitis and liver failure. |
|
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Term
|
Definition
| > 100-200 mg: peripheral neuropathy leading to ataxia |
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Term
Excess vitamin A
epiphyseal plate |
|
Definition
| If there is an excess of vitamin A in a growing child, there is rapid erosion of cartilage resulting in premature closure of the epiphyseal plate, causing Dwarfism. Vitamin A coordinate the activity between osteoblasts and osteoclasts. |
|
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Term
|
Definition
| >8000 IU: increased osteoporosis in elderly women. >10,000 IU: fetal cranio-facial, CNS or heart defects. >50,000 IU: hepatomegaly, bone thickening, blurred vision, headache. |
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|
Term
|
Definition
| > 25,000 IU: growth retardation, calcification of kidney and heart |
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|
Term
Factor V Lediden/ Thrombophilia
factor V gene |
|
Definition
| a point mutation at position 1691 in the factor V gene is associated with increased risk of thromboembolism via activated protein C (APC) resistance. mutation swaps agrginine for histidine. Predisposed to defeloping blood closts. Homozygous state has greatly increased risk (50-80X). Heterozygous: 4-8X risk |
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|
Term
Familial Alzheimer's Disease
early-onset |
|
Definition
| three genes responsible: Presenilin 1 (PSEN1): 20-70% of early-onset. PSEN2: rare. Amyloid precursor protein: 10-15%. APP is located on chromosome 21 and is also the cause of alzheimer's-like disease in Down syndrome patients. Apo E (epsilon 4) is also associated with earlier onset. epsilon 2 has a protective effect and is more common in the general population. |
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|
Term
|
Definition
| short palpebral fissure, short now, long philturm, thin upper lip. Low BW, growth delay, heart defects. |
|
|
Term
|
Definition
| low BW, coarse face, heart defects. Hepertelorism, short nose, low nasal bridge. |
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|
Term
Fragile X Syndrome
FMR1 gene at Xq27.3 |
|
Definition
| most common form of inherited mental retardation. Fragile site contains a CGG repeated motif in the 5' untranslated region of the FMR1 gene. 6 - 50 repeats is normal, >200: full mutation - prevents transcription of gene (hypermethylation) and so the RNA binding protein (FMR1 gene product) is absent. Repeats are generated by aberrant recombination. Penetrance increases with each succeeding generation (amplification of region). 1/4000 males. folate-sensitive fragile site at Xq27.3 |
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Term
Fructose Uria
Fructokinase |
|
Definition
| An absence of fructokinase causes the benign condition of fructose uria, where fructose in excreted in the urine due to an impaired ability to metabolize it. |
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Term
Galactosemia
galactose-1-phosphate uridyl transferase |
|
Definition
| the absence of galactose-1-phosphate uridyl transferase is a severe autosomal recessive disease that lease to an accumulation of toxic substance. Galactitiol, formed by the reduction of galactose, is one of these and leads to the formation of cataracts (galactitol is osmotically active). Symptoms include failure to thrive, liver enlargement, jaundice. vomiting or diarrhea following milk consumption. mental retardation common. |
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|
Term
|
Definition
| cataracts, low blood sugar. Autosomal recessive. Usually due to a deficiency in GALT, but can also be due to a deficiency of gactokinase or epimerase. |
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|
Term
Gaucher's Disease Type 1
glucocerebrosidase |
|
Definition
| Tissues accumulate glucocerebroside due to a deficiency of glucocerebrosidase - can't cleave the cerebroside-glucose linkage. Symptoms include easy bruising, fatigue due to anemia, enlargement of liver and spleen, weakness of skeleton; occasional lung and kidney impairment. early childhood to late adult onset. some success with IV enzyme replacement therapy (ceradase or cerezyme). |
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|
Term
Gaucher's Disease Type 2 and 3
glucocerebrosidase |
|
Definition
| rare. Similar to type one but a different isozyme is impacted. Type 2 is most severe - early onset with extensive brain damage |
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Term
Genetic (Hereditary) hemochromatosis
membrane glycoprotein HFE - normally interacts with transferrin |
|
Definition
| Common genetic disorder in people of western European ancestry. A defect in a membrane glycoprotein (HFE) regulating affinity of the transferrin receptor for transferrin leads to excessive absorption of iron. Cells can't take up iron from transferrin, and so produce more DMT-1. Often manifests in adulthood with symptoms of cardiomyopathy, liver cirrhosis, diabetes and athropathies (due to iron accumulation in tissues). Can also be Hepcidin-assoc (not enough - uncontrolled release of iron) or other mutations - these are rare and juvenile onset. |
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Term
Genetic Porphyrias
heme synthetic pathway |
|
Definition
| Involve defects in specific steps in heme biosynthesis, leading to accumulation of product form the previous step. Characteristic features often include photosensitivity, hair growth, accumulation of porphyrins in urine (reddish). Acute intermittent porphyria (porphobilinogen deaminase impacted) is the most common. |
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|
Term
Gigantism
epiphyseal plate |
|
Definition
| If there is an excess of Growth Hormone (somatotropin) in a growing child, gigantism results |
|
|
Term
Gilbert's syndrome
UDP-glucuronosyl transferase |
|
Definition
| a deficiency in UDP-glucuronosyl transferase (due to defects in the promoter), the rate limiting step in bilirubin glucouronide production, causes mild symptoms. Affects 5-10% of the Caucasian population. Slower clearance of unconjugated bilirubin. |
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|
Term
Glanzmann's disease
integrin |
|
Definition
| A particular integrin in not produced. Platelets cannot bind fibrinogen, and so they cannot be activated. Patients have excessive bleeding due to lack of clotting. |
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|
Term
Glucose 6-Phosphate DH deficiency
G6P DH |
|
Definition
| A deficiency/defect in this enzyme reflects a less active form or one with a shorter half-life. A common X-linked disorder found in 11% of African Americans. G6P Dh is an enzyme that produces NADPH which is necessary for glutathione reduction. A deficiency leaves the patient susceptible to oxidative stress, which can trigger an attack of hemolytic anemia. |
|
|
Term
|
Definition
| an extreme case of hyperuricemia. Inflammation of joints due to deposits of sodium urate crystals. Often found in the big toe and other joints. defects in purine matabolism (PRPP Synthetase, G6PD, or a partial HGPRTase defeciency) may predispose a patient to gout. Treatment: anit-inflammatory (colchicine), inhibition of uric acid production (allopuinol - inhibits xanthine oxidase), or increase uric acid clearance (urcosuric drugs inhibit reabsorbtion). |
|
|
Term
Hemolytic jaundice
RBC destruction |
|
Definition
| Seen in conditions with increased destruction of RBCs - too much Hb for the liver to metabolize. Increase in unconjugated bilirubin. |
|
|
Term
|
Definition
| deficiency of blood clotting factor VIII; excessive bleeding from minor traumas; internal bleeding. |
|
|
Term
Hepatocellular Jaundice
Liver |
|
Definition
| seen in liver damage in hepatitis or cirrhosis. Damaged liver can't take up bilirubin quickly enough - increased levels of unconjugated bilirubin (even at normal levels of production). May also have some release of bilirubin glucouronide due to cellular damage - possible increase in direct bilirubin. |
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|
Term
Hereditary Elliptocytosis, pyropoikilocytosis
spectrin |
|
Definition
| defects in spectrin that affect interaction within the spectrin tetramer lead to defects in the horizontal interaction. |
|
|
Term
Hereditary Fructose Intolerance
Phosphofructoaldolase B |
|
Definition
| An absence of phosphofructoaldolase B leads to the inability to metabolize glucose. A severe disorder can cause hepatic failure. Treatment is to avoid fructose in the diet. |
|
|
Term
hereditary hemochromatosis
6p21.3 (HFE gene) |
|
Definition
| autosomal recessive. 1/400 caucasions. 1/10 carrier frequency. Innapropriately high iron absorption due to mutations in the HFE gene (facilitates uptake of Tf bound Fe). Common mutations are C282Y and H63D. 87% have at least one copy of C282Y. Location: 6p21.3 |
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|
Term
Hereditary Orotic Aciduria
pyrimidine nucleotide biosynthesis |
|
Definition
| caused by a deficiency in UMP Synthase (composed of two enzymes, orotate phosphoribosyl transferase and orotidine decarboxylase), which leads to a deficiency of UTP, a lack of pyrimidines, and increased flux through the first steps of the pathway, giving an accumulation of orotic acid. Symptoms include magaloblastic anemia, growth retardation. treated with oral uridine. |
|
|
Term
Hereditary Spherocytosis
band 3 |
|
Definition
| loss of interactions between spectrin, ankyrin or band 3 leads to defects in the vertical interactions in the cytoskeleton. |
|
|
Term
Hereditary Spherocytosis
Spectrin (or Ankryn, etc) |
|
Definition
| mutations in the genes for Spectrin or Ankryn lead to a weakened interaction between the integral and peripheral proteins of the RBC membrane. This results in the loss of deformability in the RBC and they are subject to destruction in the spleen. |
|
|
Term
|
Definition
| Treated with Acyclovir (acycloguanosine), which the HSV-tyrosine kinase phosphorylates. The phosphorylated acycloguanosine functions as a DNA chain terminator. |
|
|
Term
Hexokinase deficiency
2,3-DPG |
|
Definition
| Hexokinase is the first enzyme in glycolysis. A deficiency leads to less flux through the pathway, leading to a decrease in 2,3-DPG, causing a left-shift in the O2 binding isotherm. |
|
|
Term
|
Definition
| the HIV virus binds the CD4 protein on the helper t-cells and enters them. The virus then kills the cells, leading to a breakdown of the immune system. |
|
|
Term
Holoprosencephaly
SHH (sonic hedgehog) |
|
Definition
| loss-of-function of SHH gene mutation. |
|
|
Term
|
Definition
| Factor in CHD risk. Low blood folate in associated with high blood homocysteine. Treat with three steps: diet, multivitamin, elevated (prescription) vitamin doses. |
|
|
Term
|
Definition
| An overabundance of homocysteine in the blood. For a Cysthathionine Synthase deficiency, give B6/restrict methionine. For a methionine synthase or methylene THF reductase deficiency, give folate. For a cobalamin interconversion defect or a cobalamin absorption or transport abnormality, give B12. early death due to cardiovascular problems. |
|
|
Term
Homocystinuria
Cysathionine beta-synthase (formation of cysteine from methionine) |
|
Definition
| a deficiency in this vitamin B6-dependant enzyme in recessive and manifests with eye ectopia lenitis, osteoporosis, mental retardation, and vascular thrombotic events. There are two types - vitamin responsive can be treated with supplements and vitamin unresponsive must follow a methionine restricted diet supplemented with cystine and betaine (can serve as a methyl donor) to promote remethylation of homocysteine. |
|
|
Term
Huntington's Disease
4p16.3 (huntingtin gene) |
|
Definition
| expansion of a repeat CAG (>36) in the protein coding reigon results in a polyglutaminyl tract in the protein Huntingtin. Protein is insoluable and toxic to specific neurons. Autosomal dominant. Location: 4p16.3. |
|
|
Term
Hurler Syndrome
alpha-L-iduronidase gene (4p16.3) |
|
Definition
| Autosomal recessive. unsteady gait, lost speech. Coarse facial features, spade hands, enlarged liver. urine metabolic screen positive for mucopolysaccharides (Dermatan and Heparan sulfate). Buildup of dermatan and heparn sulfate in NS (urine spillover). alpha-L-Iduronidase usually breaks them down. Low leukocyte iduonidase. fatal. |
|
|
Term
Hyperammonenia Type 1
Urea cycle |
|
Definition
| Carbamoyl phosphate synthetase I (CPI) or N-acetylglutamate synthetase deficiency. Treat the former with arginine (positive modulator for the formation of N-acetylglutamate) and the latter with carbamoyl glutamate (activates CPI). |
|
|
Term
Hyperammonenia Type 2
Urea cycle |
|
Definition
| X-linked ornithine transcarbamylase deficiency, causing elevate blood ammonia, amino acids, orotic acid, glutamine. Treated with a high a high carb, low protein diet as well as benzoic or phenylacetic acid to treat ammonia intoxication. |
|
|
Term
Hypercholesterolemia
high LDL-cholesterol |
|
Definition
| treatment for high LDL: diet low in saturated/trans fats (fat = 30% of calories). Reduce total calories. If diet isn't enough, statins reduce LDL. If diet and statins aren't enough, can supplement with a BAS. Exetimibe and phytosterols can also help reduce LDL levels moderately. |
|
|
Term
Hypertriglyceridemia
high TG, low HDL |
|
Definition
| slight higher in fat (35% of calories). Emphasis on monounsaturated fats. Low carbohydrates. If diet isn't enough, a TG lowering statin (s/a Atorvastatin) can be used. Niacin helps to raise HDL levels and also reduces the formation of small LDL and HDL - doesn't impact the total level of LDL. |
|
|
Term
|
Definition
| excess of uric acid in the circulation and urine |
|
|
Term
|
Definition
| the heart has a very small margin for hypoxia. Ischemia (reduced blood flow) leads to decreased contractions for in 10 - 20 seconds, stops in 10 min., and dies in 20. |
|
|
Term
Ineffective erythropoiesis
RBC |
|
Definition
| You will see lots of hemosiderin in the bone marrow, a hypochromatic peripheral smear, and a low reticulocyte count. |
|
|
Term
| Infant of diabetic mother |
|
Definition
| high BW (macrosomia), brain anomalies, heart defects |
|
|
Term
Insulin resistance/ Type II diabetes
GLUT 4 |
|
Definition
| can be caused by a defect in the GLUT 4 receptor. GLUT 4 functions in the facilitated diffusion of glucose and is insulin-responsive and is found in muscle and adipose tissue. (Insulin triggers the release of GLUT 4 protein to the membrane). |
|
|
Term
|
Definition
| At the early states, total iron binding capacity (increases) and serum ferritin (decreases) are impacted. Late indicators are Hb levels and MCV (low). Fatigue, weakness, anorexia, koilonychia are symptoms. There is also in increases susceptibility to infections (impaired cellular immunity). |
|
|
Term
Iron Deficiency Anemia
Hb |
|
Definition
| Microcytic, hypochromic RBCs (decrease in both MCV and MCHC). Increase in total iron binding capacity (increase in transferrin, transferrin receptor, and DMT-1) - different from anemia of chronic disease. Serum iron, ferritin, and ALA-S (regulatory enzyme for heme formation) decrease. General anemia effects: increase in serum EPO and 2,3-BPG. Bone marrow won't have iron stores (no blue when stained). You will also see an increase in reticulocytes 5 - 7 days after therapeutic iron. |
|
|
Term
Kartagener's Syndrome
Axoneme (dynein or radial spokes) |
|
Definition
| The lack of dynein or cross arms in cilia and flagella causes immotile cilia and flagella with sterility, chronic respiratory infection and malrotation of the heart (unclear why malrotation of the heart is a symptom). |
|
|
Term
Kearns-Sayre Syndrome
mtDNA deletion |
|
Definition
| multisystem disorder characterized by brain anda muscle dysfunction, progressive external opthalmoplegia, and pigmentary retinopathy. Short stature, hearing losss, mental retardatio nr dementia, and endocrinopathy. Deletions can be >40% of mtDNA. |
|
|
Term
Kernicterus
excessive bilirubin in the blood |
|
Definition
| caused by untreated jaundice - severe neurotoxic effects: athetoid cerebral palsy, severe motor delay, dysarthria, sensoneuronal hearing loss, mental retardation |
|
|
Term
Klinefelter Syndrome
47,XXY |
|
Definition
| 1/1000 newborn males. Normal face, tendency towards lond arms and legs. Small genitalia; gynecomastia. Infertility. IQ usually normal. |
|
|
Term
|
Definition
| in heme synthesis, ALA DH forms porphobilinogen from two ALAs. This enzyme has an active site zinc that is displaced by lead - enzyme deactivated (ALA appears in urine). Also inhibits protoporphyrinogen oxidase leading to the accumulation of free protoporphyrinogen IX and Zn-protoporphyrinogen IX. Ferrochelatase is also inhibited by lead (protoporphyrin IX can't be converted to heme - final step) |
|
|
Term
Lesch-Nyhan Syndrome
nucleotide salvage pathways |
|
Definition
| the lack of HGPRT prevents the slavaging of guanine and hypoxanthine, leadind to increased de novo synthesis of purine nucleotides and increased levels of uric acid. Neurological features include self-mutilation, choreoathetosis, spastciity, and mental retardation. |
|
|
Term
Leukocyte Adhesion Deficiency
integrin |
|
Definition
| Integrin is not produced properly and so leukocytes can not effectively migrate out of the blood vessel. Patients suffer fro life-threatening infections. |
|
|
Term
Lever's Hereditary Optic Neuropathy (LHON)
mtDNA point mutation (protein-encoding gene) |
|
Definition
| rare neurodegenerative disease of young adults that results in blindness due to optic ner degeneration (G11778A mutation in ND4, NADH DH subunit 4) |
|
|
Term
|
Definition
| doesn't really normalize with diet therapy. Restrict intake of trans fatty acids. Niacin and Statin (LDL < 80 to mitigate impact of Lp(a)). |
|
|
Term
|
Definition
| folic acid deficiency. Associated with a diet low in leafy vegetables. Macrocytic RBCs (MCV >90). Can cause neural tube defects and homocysteinemia. Currently supplemented in flour. |
|
|
Term
Maple Syrup Disease
BCKAD (branched chain keto acid DH) |
|
Definition
| a deficiency in the alpha-keotacid dehydrogenase complex leads to the accumulation of intermediates of the breakdown of branched chain amino acids. Causes severe mental retardation. Rare, recessive disorder in isolated asian and caucasion (Amish) communities. |
|
|
Term
Marfan Syndrome
fibrillin-1 gene (15q21.1) |
|
Definition
| Autosomal dominant, variable expressivity. Mutatuion in fibrillin-1 (FBN1) located on chromosome 15q21.1. Fibrillin-1 is an ECM protein found in elastic tissues and so effects connective tissue throughout the body. Dilated aortic root (may rupture). ectopia lentis, long fingers and body. mild joint laxity (look for "thumb sign" or "wrist sign"). beta blockers reduce the force of heart ejection, reducing pressure on the aorta. |
|
|
Term
Marfan's Syndrome
elastic fiber |
|
Definition
| Caused by poor microfibril formation in elastic fiber (microfibrils surround the amorphous elastin center). This weakens the elastic fibers and leads to a tendency to rupture the aorta and other blood vessels. |
|
|
Term
| Maternal myopathy and cardiomyopathy |
|
Definition
| MMC is due to a mutation in tRNA (leu) |
|
|
Term
|
Definition
| simialar to FAS - mental retardation a problem due to high phenylalanine/phe byproducts levels interfering with NS development. |
|
|
Term
MCAD
Medium chain acyl CoA DH |
|
Definition
| autosomal recessive. Urine has high acylglycine levels and plasma has high acylcarnitine levels. After fast, hypoglycemia, metabolic acidosis, enlarged liver. Medium chain acyl CoA DH deficiency. |
|
|
Term
MCAD (medium chain Acyl-CoA Dehydrogenase Deficiency) f
atty acid catabolism |
|
Definition
| The catabolism of medium chain fatty acids (6-12 C) is deficient due to a defect in the dehydrogenase. Symptoms (usually in the first two years) are precipitated by fasting or infection, and urine contains MCFA esters of glycine and carnitine. Treat with glucose, high carb diet. Also SCAD (short chain) and LCAD (long chain). |
|
|
Term
Megaloblastic Anemia
methionine synthase (both)/ methylmalonyl mutase (B12) |
|
Definition
| Megaloblasts are found in the bone marrow, and large RBCs in circulation (macrocytic anemia). Caused by a disturbance in DNA synthesis. Can be caused by deficits in either B12 (Pernicious anemia) or folate. Excess methylmalonic acid is found in urine in pernicious anemia only. |
|
|
Term
metabolic acidosis
glutaminase |
|
Definition
| results from the production of metabolic acids (ketoacidosis in uncontrolled diabetes is the most common) or the excessive loss of bicarbonate (s/a in diarrhea). Urea production is suppressed and ammonium is excreted directly by the kidney through the action of glutaminase (glutamine + water --> glutamate + NH4+ |
|
|
Term
Methemoglobin Anemia
methemoglobin reductase II, cytochrome b5 reductase, alpha or beta subunits |
|
Definition
| A result of any number of mutations that leads to an excessive production of Methemoglobin. Defects in methemoglobin reductase II are relatively mile, but can be induced by oxidant stress. Defects (severe or mild) or deficiency (mild) in cytochrome b5 reductase can cause symptoms. Mutations in the alpha or beta subunits in Hb can make the iron more prone to oxidase (Hb Ms). |
|
|
Term
| Mitochondrial encephalopathy, lactic acidosis, and stroke-like symptoms |
|
Definition
| MELAS is due to a mutation in tRNA (leu) |
|
|
Term
|
Definition
| Diet - exclude alcohol - and TG lowering stating (atorvastatin). |
|
|
Term
Multiple Carboxylase deficiency
biotin |
|
Definition
| results from a biotin deficiency or a defect in biotin holocarboxylase synthetase. Prevents the attachment of biotin to biotin-dependent enzymes. Symptoms include seborrheic dermatitis, anorexia, nausea, and muscular pain. |
|
|
Term
Multiple Sclerosis
myelin |
|
Definition
| multiple sclerosis is thought to be an autoimmune disorder in which the oligodendrocytes are marked for destruction by macrophages in the CNS. It is a "demyelinating disease" and results in disruption of neuronal function. |
|
|
Term
Muscular Dystrophy (again)
dystrophin (an actin assoc. ptn. Found in muscle cortical networks) |
|
Definition
| an X-linked defect causes dystrophin to be dysfunctional or absent. Dystrophin cross-links the actin filaments into a supportive network and also functions to connect the internal cytoskeleton to the external matrix. As a result, the muscle cell membrane (sarcolemma) is easily damaged (ruptures) and the disease is ultimately fatal, due to cummulative damage to cardiac and repiratory muscle cells. |
|
|
Term
Myasthenia Gravis
Ach receptors at the neuromuscular junction |
|
Definition
| An autoimmune disorder characterized by chronic progressive muscle weakness. Antibodies that block the Ach receptors at the neuromuscular junction cause a decline in the secondary synaptic cleft area and consequently the total number of receptors. There is a reduction in the muscle excitation/contraction. Can be treated with ACh esterase (AChE) blockers. |
|
|
Term
myocardial infarction
CPK isozymes |
|
Definition
| the CPK isozyme CPK-MB is elevated in MIs |
|
|
Term
| Myoclonic epilespsy with ragged red fiber |
|
Definition
| MERRF disease is due to a mutation in tRNA (lys) |
|
|
Term
|
Definition
| caused by an overproductions of GAGs during hypothyroidism. The effected area doesn't indent when you push on it. |
|
|
Term
|
Definition
| can be caused by folate or B12 deficiency, leading to insufficient nucleotide synthesis in rapidly dividing cells. |
|
|
Term
Neurofibromatosis (type I)
17q11 (NF-1 gene - tumor supressor) |
|
Definition
| autosomal dominant with variable expression. Café au lait paatches, freckling in on-sunexposed areas. Peripheral neurofibromata. Scoliosis and neurological problems common. High risk for CNS tumor (benign but problematic). |
|
|
Term
Niemann-Pick Disease
sphingomyelinase |
|
Definition
| an autosomal recessive disorder with a deficiency of sphingomyelinase (can't cleave bond between phosphate and backbone) leading to an accumulation of sphingomyelin in neurons and "foamy" reticuloendothelial cells in liver, spleen, bone marrow, and other tissues. onset in early infancy, death before age 3. Symptoms include enlarged liver and spleen, mental retardation, anemia, neurological and physical deterioration. (Never Pick your nose with a Sphinger) |
|
|
Term
|
Definition
| autosomal dominant with variable expression. 35% with mild mental retardation. Clinical overlap with Turner Syndrome - neck webbing or redundancy of skin. Cardiac anomalies. Age dependant facial features. |
|
|
Term
Obstructive Jaundice
delivery of bilirubin glucouronide |
|
Definition
| results from interference with delivery of bilirubin glucouronide to the intestine. Total bilirubin (esp. direct) increases. Bilirubin glucouronide appears in the urine - dark brown. |
|
|
Term
osteoarthritis
synovial joints |
|
Definition
| non-inflammatory degenerative arthritis that affects synovial joints. Fibrillation of articular cartilage (loss of GS and retention of fibers), proliferation of cartilage at periphery, eventual replacement of cartilage spur to form bone spurs - reduces degree of movement. |
|
|
Term
|
Definition
| a heterogeneous group of brittle-bone diseases characterized by an excessive tendency to antenatal or postnatal fractures. 1/15,000. all types due to an abnormality in type I collagen. Genes: COL1A1 (alpha-1 chain) and COL1A2 (alpha-2 chain). |
|
|
Term
Osteomalacia (adult rickets)
calcium absorption from gut |
|
Definition
| A calcium deficiency in adults (can be caused by vit. D deficiency) means that newly formed osteons do not calcify sufficiently, weakening bones. Common in pregnancy. |
|
|
Term
|
Definition
| a severe loss of bone mass with aging - the skeleton is no longer able to maintain mechanical support. Afflicts 25% of postmenopausal women and is characterized by fractures, backaches and vertebral deformities. |
|
|
Term
oxidative phosphorylation diseases
ETC chain |
|
Definition
| due to defects in nuclear or mitochondrial DNA. Symptoms include muscle cramping and weakness, fatigue, lactic acidosis, CNS dysfunction , and vision problems. Treatment often unsuccessful. |
|
|
Term
|
Definition
| Trisomy 13. 1/15,000-25,000 live births. Bilateral cleft palate. Low-set malformed ear. Renal and cardiac defects. Polydactyly. |
|
|
Term
Pearson's Syndrome
mtDNA deletion |
|
Definition
| non-neurological childhood loss of blood cells (pancytopenia) and pancreatic dysfunctions. Becomes clinically similar to Kearns-Sayre in those that survive to adulthood. |
|
|
Term
|
Definition
| niacin deficiency. Was a problem in the south where maize was a staple. Currently supplemented in flour. Four Ds: Dermatitis, diarrhea, dementia, and death. |
|
|
Term
Pernicious Anemia
B12 deficiency |
|
Definition
| Due to a deficiency in intrinsic factor (caused by a deterioration of the stomach lining due to the autor-immune disease, chronic atrophic gastritis), B12 absorption is reduced. Methylmalonyl CoA Mutase and Methionine synthase both require B12. Increased methylmalonic acid in urine. |
|
|
Term
|
Definition
| Vitamin B12 deficiency. A result of the loss of intrinsic factor or unsupplemented vegan diet. |
|
|
Term
Pernicious Anemia
Methylmalonyl CoA mutase |
|
Definition
| caused by a deficiency in methylmalonylCoA mutase (converts methylmalonyl Coal to Succinyl CoA) or a lack of vitamin B12 due to inadequate intrinsic factor (a glycoprotein secreted by the stomach required for the absorption of vitamin B12) or a strictly vegan diet |
|
|
Term
Phemphigus Vulgaris
desmoglein (a cadherin) |
|
Definition
| an autoimmune disease where antibodies to the cadherin desmoglein (found in desmosomes - extends across gap) are created, destroying the patient's desmosomes (especially in skin). This leads to severe blistering and infection. |
|
|
Term
Phenylketonuria
phenylalanine hydroxylase |
|
Definition
| phenylalanine hydroxylase normally converts phenylalanine to tyrosine. Without this enzyme, phenylalanine and its' breakdown chemicals from other enzyme routes accumulate in the blood and body tissues. Symptoms include hyperactive reflexes, mental retardation, and seizures. |
|
|
Term
Phenylketonuria (again)
phenylalanine hydroxylase |
|
Definition
| phenylalanine hydroxylase normally converts phenylalanine to tyrosine. Without this enzyme, phenylalanine and its' breakdown chemicals from other enzyme routes accumulate in the blood and body tissues. Symptoms include hyperactive reflexes, mental retardation, light pigmentation (phe --> tyr --> melanin), and seizures. Treated with a phenylalanine restricted, tyrosine supplemented diet. |
|
|
Term
Phenylketouria
phenylalanine hydroxylase or DHPR |
|
Definition
| autosomal recessive. Can't convert phenylalanine to tyrosine. High levels of Phe in blood stream. Inadequate synthesis of myelin (low IQ, decreased head size). 1/10,000. Phenylalanine hydroxyase deficiency. Can also be due to deficiency in dihydropteridine reductase (DHPR) or a biosynthetic defect in the synthesis of BH4. Phe restricted diet; L-Dopa and 5-hydroxytryptophan in case of the latter. |
|
|
Term
Phocomelia (Thalidomide embryopathy)
thalidomide |
|
Definition
| prenatal exposure to thalidomide is a phenocopy of the inherited disease, phocomelia. Causes limb shortening. |
|
|
Term
|
Definition
| an abnormal buildup of interstitial fluid in the ECM. Can be caused by protein imbalance (liver disease, starvation), blocked lymphatics (surgery, elephantiasis), increased vascular permeability, hypertension (too much hydrostatic pressure on arterial end), heart failure (too much hydrostatic pressure on venous end). |
|
|
Term
Pituitary dwarfism
epiphyseal plate |
|
Definition
| If there is a deficiency of Growth Hormone (somatotropin) in a growing child, dwarfism results |
|
|
Term
|
Definition
| amniotic tear with chronic leakage or bilateral renal agenesis causes oligohydramnios and fetal constraint, causing secondary anomalies s/a fetal growth deficiency, potter facies, limb position defects. |
|
|
Term
Prader-Willi Syndrome
SNRPN gene (15q11q13 - maternal copy only) |
|
Definition
| hyperphagia and obesity, skin picking and high pain threshold, hypotonia, mild to moderate MR, hypopigmentation, behavioral disturbances. Paternal del(15q11q13) or uniparental disomy (UPD) - maternal. Few imprinting mutations. SNRPN gene product assoc. with snRNPs (pre-RNA processing) |
|
|
Term
pseudo-hermaphroditism
SRY gene |
|
Definition
| XX male - SRY gene translocated to X chromosome due to aberrant recombination outside of the pseudoautosomal region. |
|
|
Term
|
Definition
| XY female with nearly normal phenotype. Can't undergo puberty. |
|
|
Term
Pyruvate Kinase deficiency
2,3-DPG |
|
Definition
| Pyruvate Kinase is at the end of the glycolysis pathway. A deficiency leads to higher concentration of 2,3-DPG due to a slower conversion of PEP to pyruvate, causing a right shift in the O2 binding isotherm. |
|
|
Term
Retinoblastoma
RB gene on chromo. 13 |
|
Definition
| Two Hit Hypothesis: a mutation in one copy of the RB gene is inherited, and the second copy develops a somatic mutation. This allows the cell to proliferate in an uncontrolled manner. Retinoblastoma tumors are typically only found in young children. |
|
|
Term
| Retinoic Acid Embryopathy |
|
Definition
| anterolateral displacement of hair whorl, micrognathia, U-shaped palate. Down-slanting palpebral fissures, microtia or anotia. Hydrocephalus possible. Heart and limb defects. |
|
|
Term
rheumatoid arthritis
synovial joints |
|
Definition
| inflammatory autoimmune disease. Attacks synovial membrane and joint cartilage - membrane thickens (inflamed) and synovial fluid production increases. Pannus of tissue forms across cartilage and erodes away cartilage, exposing bone which eventually fuses across joint. |
|
|
Term
Rickets
calcium absorption from gut |
|
Definition
| a lack of vitamin D in growing children leads to a calcium deficiency (vit. D controls absorption of calcium from gut), and there is no mineralization of cartilage in the epiphyseal plate and bone osteoid. This leads to weak bones and is characterized by "bow legs". |
|
|
Term
Rothmund-Thomson
RecQ5 helicase |
|
Definition
| Recessive mutation in RecQ5 helicase- accelerated aging. Cardiovascular disease, arthritis, cancer. Chromosomal and genomic instability. |
|
|
Term
sarcomas and gliomas
CDK4 |
|
Definition
| CDK4 has been shown to be amplified in sarcomas and gliomas |
|
|
Term
|
Definition
| severe combined immunodeficiency disorder can be caused by adenosine deaminiase (ADA) deficiency. ADA catalyzes the irreversible deamination of adenosine to inosine, and deficiency results in cytoxic accumulation of dATP and deoxyadenosine in immature lymphocytes. typically treated with the enzyme imbedded in a PEG tablet; possible bone marrow transplant. experimental gene therapy. |
|
|
Term
|
Definition
| Vitamin C (ascorbate) is a necessary cofactor for prolyl hydroxylase. This enzyme hydroxylates proline so that it may form hydrogen bonds in the collagen fibrils. |
|
|
Term
Severe Combined Immunodeficiency Syndrome (SCID)
purine metabolism |
|
Definition
| a deficiency in adenosine deaminase can cause a deficit of both T and B cells, possibly due to a buildup of dATP which inhibits ribonucleotid reductase (and hence DNA synthesis). A deficiency of purine nucleoside phosphorylase can induce a deficiency of T-cells only. possibly due to an accumulation of dGTP, inhibiting the reduction of pyrimidines by ribonucleotide reductase. |
|
|
Term
|
Definition
| A hydrophillic glutamine (Glu 6) is substituted for a hydrophobic valine (Val 6), creating a hydrophobic spot on the outside of the HbS molecule. This patch inserts into a hydrophobic pocket created by Ala 70, Phe 85, and Leu 88 on another molecule (deoxy form only) and begins to polymerize. Polymerization in affected by solubility (HbS is less soluable than HB), pO2 (likely at <40 torr), and an elevated body temperature. Disulfide bridges form between actin filaments if any of these factors last too long. |
|
|
Term
|
Definition
| Iron accumulates in the mitochondria because there is a block in the ETC at complex III, which leads to excess O2. This causes Fe2+ to be converted to Fe3+ before it reaches ferrochelatase - protoporphyrin doesn't get converted to heme. |
|
|
Term
skeletal dysplasias
FGFR3 |
|
Definition
| skeletal dysplasias of variable severity - achondroplasia, hypochondroplasia, and thanatophoric dysplasia. Different mutations - related/overlapping conditions. |
|
|
Term
|
Definition
| same diet as for lowering TG, weight reduction, exercise, TG-lowering statin, Niacin or Fibrate if TG>1000. |
|
|
Term
Smith-Magenis Syndrome
17p11.2 |
|
Definition
| deletion at 17p11.2. psychological disturbances: hyperactivity, behavioral problems (most). Self-injurious behavior (2/3). Insertion of foreign bodies (2/3). Head banging (2/3). Ocular abnormalities: myopia, retinal deachments, strabismus, iris anomalies. Neurological abnormalites: self-hugging, periperal neuropathy, and sleep disturbances. |
|
|
Term
|
Definition
| disorder (mutation) of HOX-D13 |
|
|
Term
Tay Sachs Disease
lysosome |
|
Definition
| a lysosomal storage disease where a deficiency in hexosaminidase A leads to an accumulation of GM2-ganglioside in the lysosomes. This causes motor and mental impairment, and is most common in those of northeast european Jewish ancestry. |
|
|
Term
Tay Sachs Disease (again)
hexosaminidase (beta-N-acetylhexosaminidase) |
|
Definition
| An autosomal recessive lysosomal storage disease where a defect in hexosaminidase (gangliosides that end with GalNAc (GM2) cannot be degraded) leads to an accumulation of GM2-ganglioside in the lysosomes. This causes motor and mental impairment, and is most common in those of northeast european Jewish ancestry. Death by age 2 |
|
|
Term
| Thiamine deficiency transketolase |
|
Definition
| Thiamine deficiency can be diagnosed by an increase in erythrocyte transketolase activity observed upon addition of thiamine pyrophosphate. |
|
|
Term
Thiamine deficiency
transketolase |
|
Definition
| complete extra set of chromosomes. 20% of chromosomally abnormal miscarriages. Early spontaneous abortion, low birth weight, small trunk to head size, syndactyly. Paternal Triploid: underdeveloped embryo with trophoblastic disease. Maternal triploid: developed embryo, underdeveloped placenta. |
|
|
Term
|
Definition
| most commonly identified trisomy in abortuses (30% of all autosomal aneuploidy in abortuses). |
|
|
Term
|
Definition
| most commonly 46,XX with testicular and ovarian tissue. |
|
|
Term
Turner's Syndrome
meiosis |
|
Definition
| single X chromosome (45,X). 95-98% abort spontaneously due to vascular abnormalities or fluid imbalance. Lymphedema biggest problem in liveborns. Webbing of neck, short stature, broad chest and widely spaced nipple. Streak ovaries, infertility, amenorrhea. |
|
|
Term
Type I diabetes
pancreatic cells |
|
Definition
| Insulin is not produced by the pancreas, impacting glucose utilization and insulin-dependant functions. Increase in adipose lipase, Acetyl-CoA carboxylase falls (not making F.A.s). Untreated diabetics produce excessive ketone bodies and their breath may have acetone. |
|
|
Term
Type I dyslipidemia
chylomicron |
|
Definition
| A deficit in Lipoprotein Lipase causes elevated TG levels |
|
|
Term
Type II Diabetes
glucose transport/utilization |
|
Definition
| Insulin is produces but the effects of insulin on glucose transport/utilization are impaired (mech. unknown). Other insulin-dependent functions are preserved - Acetyl-CoA carboxylase is stimulated to make fatty acids. Eventually, pancreas becomes resistant to glucose and stops responding with insulin, and can no longer be reversed with diet. Obesity is a major risk factor. Untreated diabetics produce excessive ketone bodies and their breath may have acetone. |
|
|
Term
Type IIa dyslipidemia
LDL (beta) |
|
Definition
|
|
Term
Type IIb dyslipidemia
LDL and VLDL |
|
Definition
|
|
Term
Type III dyslipidemia
IDL (dys-beta) |
|
Definition
| elevated LDL and TG - problem with the conversion of IDL. Causes yellowish eruptions (cholesterol) on elbow, ankles. |
|
|
Term
|
Definition
| elevated TG - can go as high as 800 (norm - 160) |
|
|
Term
Type V dyslipidemia
chylomicron and VLDL |
|
Definition
| elevated TG due to a deficit of production of Apo CII - defective removal of TGs from chylomicrons and VLDL. TGs very high - 1500+. Fibrate drugs induce the synthesis of Apo CII, reduce the synthesis of ApoCIII, and increase Lipoprotein Lipase activity and so are a good choice for treatment. |
|
|
Term
vitamin D resistant rickets.
X (PHEX gene) |
|
Definition
| low blood and high urinary phosphate levels, short stature, and bone defects. Defects in the PHEX gene on the distal portion of the short arm of the X chromosome. 1/20,000 males. |
|
|
Term
Waardenburg Syndrome, type 1
PAX3 (human analog: HuP2) |
|
Definition
| loss-of-function of PAX3 gene mutation. Hearing problems (cochlear deafness), white forelock, iris heterochromia or hypochromia. |
|
|
Term
warfarin/cumadin treatment
osteocalcin |
|
Definition
| warfarin/cumadin is used for anticoagulate therapy (interferes with the carboxylation of glutamic acid) but interferes with the production of osteocalcin, which prevents calcium deposition and can lead to severe bone disorders. |
|
|
Term
Werner's Syndrome
WRN helicase |
|
Definition
| Recessive mutation in WRN helicase- accelerated aging. Cardiovascular disease, arthritis, cancer. Chromosomal and genomic instability. |
|
|
Term
Wernicke-Korsakoff syndrome
transketolase defect, thiamine deficiency |
|
Definition
| This results from chronic thiamine deficiency coupled with defective transketolase (reduced affinity for TPP). Symptoms include weakness or paralysis and impaired mental function. |
|
|
Term
Williams Syndrome
Elastin (ELN) gene at 7q11 |
|
Definition
| autosomal dominant but mostly de novo mutations. Overfriendliness; very verbal but cognitively impaired. 75% with mental retardation. SVAS (supravalvular aortic stenosis). Elastin arteriopathy. Full lips, short nose, broad nasal tip. |
|
|
Term
Xanthinuria
catabolism of purines |
|
Definition
| a deficiency in xanthine oxidase (converts xanthine to uric acid) causes increased excretion of xanthine and hypoxanthine, and a decrease in uric acid. May result in xanthine lithiasis (kidney stones). |
|
|
Term
Zellweger Syndrome
peroxisomes |
|
Definition
| Mutations in the PXR1 gene product, a receptor which imports enzymes into the peroxisomes. Problems in prenatal dev., enlarged liver, high levels of iron and copper in blood, muscle and vision abnormalities. Death by age 6. |
|
|
