Biochem - Final - Diseases and Conditions - Part 3

davidwurbel7's version from 2015-04-19 09:54


Question Answer
Presence of gallstones in the gallbladder may lead to an inflammatory condition characterized by retention of bile in the gallbladder and often secondary infection by intestinal microorganisms, predominantly Escherichia coli and Bacteroides speciesAcute Cholecystitis
Presence of gallstones in the common bile duct and may lead to lipid malabsorption leading to deficiency of essential fatty acids and vitamin A,D,E, and KCholedocholithiasis
Most common cause of female pseudohermaphrodoitism. Deficiency of 21-hydroxylase. Normal ovarian development but masculinization of external genitalia (clitorial enlargement and labial fusion) due to excess androgens.Congenital Adrenal Hyperplasia
Autosomal recessive, loss-of-function mutation in the gene encoding MTPAbetalipoproteinemia
Plasma levels of cholesterol and triglycerides are extremely low. Chylomicrons, VLDLs, LDLs, and Apo B are undetectable in plasma. It presents usually in early childhood with diarrhea and failure to thrive due to lipid malabsorption. Defects in the absorption and transport of fat-soluble vitamins. Markedly deficient in vitamin E, mildly to moderately deficient in vitamin A and vitamin K. It is characterized by spinocerebellar degeneration, pigmented retinopathy, and acanthocytosisAbetalipoproteinemia
Deficiency of LPL, abnormal LPL, or Apo C-II deficiency causing inactive LPLFamilial Lipoprotein Lipase (LPL) Deficiency
Manifests in childhood with recurrent episodes of severe abdominal pain due to acute pancreatitis. Physical examination: lipemia retinalis, eruptive xanthomas, hepatosplenomegaly, hypertriacylgerolemia with fasting TAG levels are almost invariable >1000 mg/dLFamilial Lipoprotein Lipase (LPL) Deficiency
Oxidation of Apo B-100 by oxidative species causes the formation of plaguesAtherosclerosis
Excess accumulation of lipids within a macrophage using scavenger receptor that results in the formation of a form cellAtherosclerosis
Formation and accumulation of collagen fiber made by smooth muscle cells in the blood vessel walls can impair blood flow and eventually can form thrombi/emboliAtherosclerosis
Caused by a large number (>900) of mutations in the LDL receptor gene, homozygotes being much more affected than heterozygotes, homozygous present in childhood with cutaneous xanthomas on the hands, wrists, elbows, knees, heels, or buttocks and accelerated atherosclerosis, which can result in disability and death in childhood. Total LDL-C levels are usually >500 mg/dL and can be higher than 1000 mg/dLFamilial Hypercholesterolemia
Due to mutation in ATP-binding cassette (ABC) transporter family (ABCG5 and ABCG8) causing an increased absorption of plant sterols in intestine and reduced transport of sterols into bile by the liverSitosterolemia
An increased plasma and tissue levels of sitosterol and other plant sterols, elevated plasma levels of LDL cholesterol, development of tendon xanthomas as well as premature atherosclerosis, episodes of hemolysis due to incorporation of plant sterols in RBC membranes, responds to dietary restriction of cholesterolSitosterolemia
Elevated levels of VLDL in the blood. Moderately elevated plasma triglycerides and a modest elevation of cholesterolFamilial Hypertriacylglycerolemia
Due to mutations in the gene encoding ABCA1, Low plasma HDL-C levels (<5 mg/dL) and extremely low circulating levels of apoA-I; Cholesterol accumulation in the reticuloendothelial system, resulting in hepatosplenomegaly and pathognomonic enlarged, grayish yellow or orange tonsilsTangier Disease
Free cholesterol in circulating lipoproteins is greatly increased. Lack of normal cholesterol esterification. Plasma concentrations of cholesterol esters and lysolecithin are low. Abnormal LDL and VLDL are found in circulation. Progressive corneal opacification due to the deposition of free cholesterol in the lens, very low plasma levels of HDL-C (usually <10 mg/dL), and variable hypertriglyceridemiaFamilial Lecithin Cholesterol Acyl Transferase (LCAT) Deficiency
Reduced activity of HMG-CoA reductase. Decreased activity of LDL-receptors and increase in the serum total cholesterol concentration. Promotes LDL oxidation. Hypertriacylglycerolemia. Decreased hepatic lipase enzyme activity and elevated levels of HDL2 particles. Decreased activity of CETP and excess levels of cholesteryl esters in HDL3. Predisposed to atherosclerotic coronary artery diseaseHypothyroidism
Increased activity of the HMG-CoA reductase. Increased bile excretion of cholesterol. Increased LDL receptor gene expression. Levels of total cholesterol, LDL cholesterol, apolipoprotein B and Lp(a) tend to decrease, Triglyceride levels remain unchanged; decreased levels of HDL2 particles. Increased activity of CETP and increased catabolism of HDL3Hyperthyroidism
Deficiency of medium-chain fatty acyl CoA dehydrogenase. The C8–C12 fatty acids and their esters accumulate in tissues to cause toxicity. Non-ketotic or hypo-ketogenic hypoglycemia due to limitation of ketone body formation and C8-C12 dicarboxylic acids increase in the blood. Profound hypoglycemia during fasting, decrease in pyruvate carboxylase activity due to decreases in acetyl CoA. Treatment is IV glucose.Medium-chain Fatty Acyl CoA Dehydrogenase (MCAD) Deficiency
Muscle ache; mild to moderate muscle weakness. Rhabdomyolysis and myoglobinuria upon exercise. Accumulation of LCFAs in tissues. Severe cases lead to hypoketotic hypoglycemia, hyperammonemia, and death. Episode provoked by prolonged exercise especially after fasting, cold, or associated stress. Symptoms may be exacerbated by high fat, low-carbohydrate diet. Muscle biopsy shows elevated muscle triacylglyceride detected as lipid droplets in cytoplasm. Wasting of acyl-carnitine in urineCarnitine Deficiency
Accumulation of very long chain fatty acids (VLCFA) and branched chain fatty acids (BCFA), high levels of copper and iron in the blood and decreased levels of plasmalogens and bile acids, liver and kidney dysfunction with hepatomegaly, severe neurologic defects, hypomyelination, craniofacial and skeletal malformationsZellweger Syndrome
Peroxisomal phytanic acid hydroxylase deficiency. Buildup of phytanic acid and its derivatives in the plasma and tissues. Cerebellar ataxia, retinitis pigmentosa, and chronic polyneuropathyRefsum Disease
Sudden vomiting 2-6 hours after ingestion, followed by sever severe hypoglycemia leading to convulsions, coma, and death. Found in Jamaica and West Africa. Unripe Ackee fruit contains high levels of hypoglycin A. Hypoglycin A is metabolized to produce methylenecyclopropylacetic acid (MCPA) which interferes with transport of long-chain fatty acids into the mitochondria, and it also inhibits acyl-CoA dehydrogenasesJamaican Vomiting Sickness
Defective Hexosaminidase A enzyme, accumulation the ganglioside GM2. Commonly seen in Ashkenazi Jews. Cherry red macula, blindness, deafness, and unable to swallow. Muscles atrophy leads to paralysisTay-Sachs Disease
Inactivation of both hexosaminidase A and B activity. Accumulation of both GM2 and globoside. Cherry red macula, blindness, deafness, and unable to swallow. Muscles atrophy leads to paralysis Sandhoff Disease
Deficiency of alpha-galactosidase A. Ceramide trihexoside (globotriaosylceramide) accumulates. Kidney complications are a common and serious effect. Renal insufficiency and renal failure may worsen throughout life. Angiokeratomas (tiny, pink, painless papules) and also episodes of intense, excruciating, burning pain, felt initially in the hands and feet and radiating to other parts of the body. Hypertension and cardiomyopathy are commonly observedFabry Disease
Deficiency of the enzyme glucocerebrosidase. Incidence is high in Ashkenazi Jews. Cytoplasm is blue-gray with striations or a “wrinkled tissue paper” quality. Hepatosplenomegaly, anemia, thrombocytopenia and leukopenia. Serious convulsions, hypertonia, myoclonus, dementia, ocular muscle apraxiaGaucher's Disease
Complete absence of sphingomyelinase enzyme. Hepatosplenomegaly, unsteady gait (ataxia), slurring of speech (dysarthria), and discoordinated swallowing (dysphagia). Foam cells present in bone marrow aspirates and in macrophages and monocytes. Cherry red macula.Niemann-Pick Disease
Only hyperammonemia is seen leading to neurological effectsCarbamoyl Phosphate Synthetase I Deficiency
X-linked recessive condition, high levels of carbamoyl phosphate seen with hyperammonemia and high glutamine levels occurring as carbamoyl phosphate builds up, oroticaciduria, mental retardation if untreated in individualsOrnithine Transcarbamoylase Deficiency
Citrullinemia seenArgininosuccinate Synthetase Deficiency
Argininosuccinicaciduria seenArgininosuccinate Lyase Deficiency
HyperargininemiaArginase Deficiency
Due to liver disease and the shunting of blood from the portal system leading to elevated levels of circulatory ammoniaAcquired Hyperammonemia
Due to defective PAH gene (phenylalanine hydroxylase gene). Accumulation of phenylalanine in the blood that is well above the normal concentration. Appears normal at birth. Gradually develops varying degrees of irreversible mental retardation if not diagnosed or treated within the first month of life. Baby develops tremors, seizures, eczema, and hyperactivity "musty or mousy odor“ of baby's sweat and urineClassical Phenylketonuria (PKU)
Expectant mother having PKU failing to maintain low-phenylalanine levels will results in babies born with congenital heart disease, growth retardation, microcephaly and mental retardationMaternal Phenylketonuria (PKU)
Defective dihydropteridine reductase (DHPR) which causes deficiency of BH4. Progressive neurological manifestation and eventual death (usually in first 2 years of life) due to deficiency of neurotransmitter activityNon-classical Phenylketonuria (PKU)
Deficiency of the enzyme fumarylacetoacetate hydrolase, is the most severe form of tyrosinemia. The acute form is associated with liver failure, a cabbage like body odor, renal tubular dysfunction, rickets, polyneuropathy, accumulation of fumarylacetoacetate and maleylacetoacetate, both of which are alkylating agents and can lead to DNA alkylation and tumorigenesis, death generally occurs within first year of lifeHereditary Tyrosinemia type 1 (Hepatorenal Tyrosinemia or Tyrosinosis)
Autosomal recessive deficiency of homogentisic acid 1,2-dioxygenase (homogentisic acid oxidase or homogentisate oxidase). Homogentisic acid accumulates in the body fluids. Quinone derivative accumulates over the cartilage. Oxidized pigments are deposited in bones, connective tissue, sclera, skin and elsewhere (Ochronosis). Low back pain, Ochronotic arthritis, Presence of dark urine prior to development of other signs. Foci of gray-brown scleral pigment and generalized darkening of ear develop after 30 years of ageAlkaptonuria (Alcaptonuria)
Decreased metabolism of tyramine, elevated tyramine will release norepinephrine. Usually occurs in patients taking MAO Inhibitors. Effects includes vasoconstriction, increased heart rate, increased blood pressure, palpitation, excessive sweating, headacheThe Cheese Effect
Flushing and diarrhea are two most common symptoms. Patient may also show signs and symptoms of niacin deficiency (Pellagra). 5-HIAA seen in urinary analysis.Carcinoid Syndrome
Defect in cystathionine-beta-synthase causes the accumulation of homocysteine which can be converted to methionine, hence will lead to elevation of both homocysteine and methionine; Excessive blood clotting in the arteries and veins increases the risk of strokes and heart attack, signs similar to Marfan’s syndrome, rapid bone loss (osteoporosis), and mental retardation, damage to the neuronal network of the retina, and even loss of vision, lens dislocation is commonly seen generally in inferomedial direction; Treated with pyridoxine supplementationClassic Homocysteinemia
Defect or deficiency of methionine synthase, methyl-cobalamin or folate and its derivatives causes accumulation of homocysteine and possibly show decreased levels of methionine; Excessive blood clotting in the arteries and veins increases the risk of strokes and heart attack, signs similar to Marfan’s syndrome, rapid bone loss (osteoporosis), and mental retardation, damage to the neuronal network of the retina, and even loss of vision, lens dislocation is commonly seen generally in inferomedial direction; Treated with betaine supplementation Non-Classic Homocysteinemia
High uric acid in the blood due to renal failureHyperuricemia Under Secretor
High uric acid in the blood due to genetic defects in PRPP synthetase, specific enzyme defects like defect in hypoxanthine-guanine phosphoribosyl transferase, glucose-6-phosphatase or secondary to diseases such as cancer, psoriasis, cancer chemotherapy or radiotherapyHyperuricemia Over Producer
Serum urate levels exceed the solubility limit, monosodium urate crystalizes in soft tissues and joints and causes an inflammatory reaction, gouty arthritis. Crystals have birefringence (reflect two colors when exposed to polarized light) Crystals first appear in first metatarsal-phalangeal jointGout
Defect in hypoxanthine-guanine phosphoribosyl transferase (HGPRT). rise in intracellular PRPP, Self-mutilation, decreased IQ, neurological signs such as choreoathetosis and spasticity. Frequent episodes of hyperuricemia, uric acid lithiasis and uric acid crystals in urineLesch–Nyhan Syndrome
Deficiency of glucose-6-phosphatase. Secondary to enhanced generation of the PRPP precursor ribose 5-phosphate along with lactic acidosisVon Gierke Disease
Deficiency of adenosine deaminase (ADA). Accumulation of dATP in lymphocytes which feedback inhibits ribonucleotide reductase. B cells and T cells are sparse and dysfunctional. Severe combined immunodeficiency disease (SCID). Patients suffer from devastating fungal, bacterial and viralAdenosine Deaminase Deficiency
Deficiency of both orotate phosphoribosyltransferase and orotidylate decarboxylase. Metabolic acidosis and megaloblastic anemia which does not responds to administration of cobalamin or folic acid. Oral administration of uridine is used as treatmentOrotic Aciduria Type I
Deficiency only of orotidylate decarboxylase. Metabolic acidosis and megaloblastic anemia which does not responds to administration of cobalamin or folic acid. Oral administration of uridine is used as treatmentOrotic Aciduria Type II

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