Biochemistry Block 3 Diseases (Pt. 1)

nupiwowu's version from 2015-08-02 21:14


Question Answer
Autosomal recessive, loss-of-function mutation in the gene encoding MTTP (microsomal triglyceride transfer protein).Abetalipoproteinemia
Defects in the absorption and transport of fat-soluble vitamin. Vitamin E deficiency. Plasma levels of cholesterol and triglycerides are extremely low. Chylomicrons, VLDLs, LDLs, and apoB are undetectable in plasma. It presents usually in early childhood with diarrhea and failure to thrive due to lipid malabsorption. Spinocerebellar degeneration (long neurons), pigmented retinopathy, and acanthocytosis.Abetalipoproteinemia
Inflammation and ischemia of pancreatic tissue lead to acinar cell damage, abnormal activation of trypsin inside the acinar cells. Trypsin then activates the other proteolytic enzymes and starts a self-sustaining cycle of digestion of pancreatic tissues.Acute Necrotizing Pancreatitis
Flushing and diarrhea are two most common symptoms. Diagnosed by measuring urine or plasma serotonin or its metabolite in urine. The measurement of urinary 5-HIAA (High Levels) is most frequently used.Carcinoid Syndrome
Muscle ache; mild to moderate muscle weakness. Rhabdomyolysis and myoglobinuria upon exercise. 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.Carnitine Deficiency
Muscle specific Carnitine palmitoyl transferase II (CPT II, also called as CAT II) deficiencyCarnitine Deficiency
Accumulation of LCFAs in tissues and wasting of acyl-carnitine in urine can produce cardiomyopathy, skeletal muscle myopathy, encephalopathy, and impaired liver function.Carnitine Deficiency
40 (fatty female at forty !!!). Asymptomatic symptoms or may presents with feeling of abdominal fullness (distention), flatulence, increased satiety, and some other non-specific abdominal symptoms. Rigors & ChillsCholesterol Gallstones
Defective chloride channel, dry and thickening of exocrine pancreatic secretions, inability of pancreatic enzymes to enter into intestinal lumen to digest dietary proteins, lipids and carbohydrates.Cystic Fibrosis
Defect in the transport of cystine and the basic amino acids (arginine, lysine, ornithine) across both intestinal and renal epithelial cells. The most serious problem is insolubility of cystine, which can form kidney stone and its consequences.Cystinuria
Excess beta-oxidation depletes liver NAD+ and acetyl CoA saturates TCA cycle and decreases TCA cycle due to decreased NAD+.This shunts acetyl CoA towards ketone body formation where the flux is towards utilization of NADH + H, ketone bodies increase. Acetoacetic acid and 3-hydroxybutyric acid (ketone bodies) decrease blood pH and hence leads to metabolic acidosis and its consequences. Acetone is volatile and hence exhaled giving acetone smell to breath (fruity odor).Diabetic ketoacidosis
Accumulation of Globosides/Globotriaosylceramide. Reddish-purple skin rash. Kidney and heart failure. Burning pain in lower extremities. Full symptoms only in males; X-linked recessiveFabry Disease
α-Galactosidase A deficiencyFabry Disease
PAin is one of the more common symptoms . Angiokeratomas (tiny, painless papules that can appear on any region of the body, but are predominant on the thighs, around the belly-button, buttocks, lower abdomen, and groin) are a common symptom.Fabry Disease
Glycolipid (ceramide trihexoside A.K.A globotriaosylceramide) accumulate within the blood vessels, other tissues and organs. Fabry Disease
Mutations in the LDL receptor gene. Total LDL-C levels are usually >500 mg/dL and can be higher than 1000 mg/dL. Arcus senilis corneae, xanthelasma palpebrarum, tendon xanthomaFamilial Hypercholesterolemia
Patients present in childhood with cutaneous xanthomas on the hands, wrists, elbows, knees, heels, or buttocks. Accelerated atherosclerosis, which can result in disability and death in childhood.Familial Hypercholesterolemia
Elevated levels of Low density lipoprotein cholesterol (LDL-C) due to an increase in the production of LDL from IDL and a delayed catabolism of LDL from the blood. It is characterized by elevated plasma levels of LDL-C (usually 200–400 mg/dL) and normal levels of triglyceride.Heterozygous Familial Hypercholesterolemia
Autosomal recessive mutations in the gene encoding the plasma enzyme LCAT. The proportion of free cholesterol in circulating lipoproteins is greatly increased (from ~25% to over 70% of total plasma cholesterol) in this disorder.Familial Lecithin:Cholesterol Acyltransferase (LCAT) Deficiency
Lack of normal cholesterol esterification impairs the formation of mature HDL particles and therefore results in rapid catabolism of circulating apoA-I. Plasma concentrations of cholesteryl esters and lysolecithin are low. Abnormal LDL (lipoprotein X) and VLDL is (β-VLDL) is 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 hypertriglyceridemia.Familial Lecithin:Cholesterol Acyltransferase (LCAT) Deficiency
Accumulation of ceramide. Dermatitis, skeletal deformation, mental retardation, hoarseness of voice. Painful and progressive joint deformity.Farber Disease
Slow clearance of chylomicrons and VLDL leading to elevation of chylomicrons and VLDL. The fasting plasma is turbid, and if left at 4˚C develops a creamy supernatant. Fasting TAG levels are almost invariable >1000 mg/dL. It manifests in childhood with recurrent episodes of severe abdominal pain due to acute pancreatitis. Physical examination: lipemia retinalis, eruptive xanthomas, hepatosplenomegaly.Familial Lipoprotein Lipase (LPL) Deficiency (Chylomicronemia Syndromes)
Elevation of chylomicrons (predominantly) and VLDL. Hepatosplenomegaly. Lipemia Retinalis. Eruptive xanthomas, which are small, yellowish-white papules, often appear in clusters on the back, buttocks, and extensor surfaces of the arms and legs. These typically painless skin lesions may become pruritic (itchy).Familial Lipoprotein Lipase (LPL) Deficiency (Chylomicronemia Syndromes)
Subcutaneous nodules of lipid-laden cells and tissue granulomas.Farber Disease
Ceramidase deficiencyFarber's Disease
Accumulation of glucocerebrosides/glucosylceramide. Hepatosplenomegaly, osteoporosis of long bones, CNS involvement in rae infantile and juvenile formsGaucher Disease
Glucocerebrosidase A.K.A β-Glucosidase deficiencyGaucher Disease
Cells have a distinctive appearance. The cytoplasm is blue-gray with striations or a “wrinkled tissue paper” quality. Patients usually bruise easily (due to low levels of platelets) and experience fatigue (Anemia) due to low numbers of red blood cells. Neurological symptoms include: serious convulsions, hypertonia, myoclonus, dementia, ocular muscle apraxia.Gaucher Disease
Autosomal recessive defect in (transport) intestinal absorption and kidney reabsorption of neutral amino acids including tryptophan. Patients end up with Niacin deficiency and pellagra like symptoms (Dermatitis, Dementia, and Diarrhea).Hartnup Disease
Two deficiencies that lead to Tay-Sach's diseaseHex A & Sandhoff Activator Protein Deficiencies.
Usually caused by liver diseases, such as viral hepatitis, or excessive alcohol consumption. Cirrhosis of the liver is formed, followed by a shunt of blood directly to the vena cava, resulting in decreased filtration of blood in the liver, which leads toHyperammonemia
Acute viral hepatitis, decreased urea cycle and increased accumulation of ammonia. The hepatic changes in chronic cases may be due to shunting of portal blood directly into systemic circulation and does not have access to the liver. The detoxification of ammonia is therefore, severely impaired leading to elevated levels of circulatory ammonia and hence its consequences.Hyperammonemia
Accumulation of Hypoglycin A leading to methylenecyclopropylacetic acid (MCPA), which interferes with the transport of long-chain fatty acids into the mitochondria`, and it also inhibits acyl-CoA dehydrogenases~ involved in beta-oxidation of fatty acids. Inhibition of beta-oxidation leads to decrease in ATPs and hence decrease in gluconeogenesis.Jamaican vomiting sickness
Ingestion of unripe Ackee fruit leads sudden vomiting 2-6 hours after ingestion, followed by severe hypoglycemia leading to convulsions, coma, and death.Jamaican vomiting sickness
Hypoglycin A is toxic if ingested and is the causative agent of Jamaican vomiting sickness.Jamaican vomiting sickness
Profound fasting hypoglycemia (due to decreased gluconeogenesis). Low to absent ketone bodies (low or absent acetyl CoA formed as there is low or absent beta-oxidation). Increase in C8-C12 acyl carnitines in the blood. Episodes may be provoked by overnight fast in an infant or by flu in older child. Lethargy, coma and death if untreated.Medium-Chain Fatty Acyl CoA Dehydrogenase (MCAD) Deficiency
Impairs oxidation of medium chain (C8–C12) fatty acids. The C8–C12 fatty acids and their esters accumulate in tissues to cause toxicity. Spillover of C8–C12 acylcarnitine species into the blood Medium-Chain Fatty Acyl CoA Dehydrogenase (MCAD) Deficiency
During fasting, hypoglycemia can become profound due to lack of ATPs to support gluconeogenesis. Decreased fatty acid oxidation decreases acetyl CoA which decreases pyruvate carboxylase activity (decreased gluconeogenesis). Decreased levels of acetyl CoA also limits ketone body formation. Non-ketotic or hypo-ketogenic hypoglycemia should be strongly associated with a block in hepatic beta-oxidation (defect).Medium-Chain Fatty Acyl CoA Dehydrogenase (MCAD) Deficiency
Accumulation of sphingomyelin. Hepatosplenomegaly, neurodegenerative course (Type A), cherry red-macula. Characteristic foam cells present in bone marrow aspirates and in macrophages and monocytes.Niemann-Pick Disease
Sphingomyelinase deficiencyNiemann-Pick Disease
Elevated levels of ammonia and glutamine leads to neurotoxic effects. Mental retardation is seen in untreated individuals. Elevated levels of orotic acid is seen in this disease.Ornithine Transcarbamylase (OTC) deficiency
Deficiency of ________ leads to accumulation of carbamoyl phosphate in mitochondria which diffuses into cytoplasm, where it condenses with aspartate, a reaction catalyzed by cytoplasmic aspartate transcarbamoylase (ATC) ultimately forming orotate (orotic acid). Ornithine Transcarbamylase (OTC) deficiency
Deficiency of peroxisomal phytanic acid hydroxylase deficiency.Refsum Disease
Impaired α-oxidation of phytanic acid resulting in buildup of phytanic acid and its derivatives in the plasma and tissues. This leads to severe symptoms related to brain, eyes and nerves (cerebellar ataxia, retinitis pigmentosa, and chronic polyneuropathy). Refsum Disease
Treatment: low-phytanic acid diet (restriction of dairy products and avoid consumption of ruminant meatRefsum Disease
Accumulation of Gangliosides GM2 & Globosides. Rapid, progressive and fatal neurodegenerative, blindness, cherry red macula, muscular weakness seizures with visceral involvement. Sandhoff Disease
Hexosaminidase B deficiencySandhoff Disease
Mutation of the HexB gene, and production of a defective β- subunit, leads to inactivation of both hexosaminidase A and B activity.Sandhoff Disease
Deficiency in the activator protein for Hexosaminidase A, leads to decreased hexosaminidase A activity and GM2 ganglioside accumulates in the lysosomes. Patients present with Tay-Sachs disease symptomsSandhoff Activator Disease
Mutation in ATP-binding cassette (ABC) transporter family (ABCG5 and ABCG8).Sitosterolemia
This disease is due to increased absorption of plant sterols in intestine and reduced transport of sterols into bile by the liver. This results in increased plasma and tissue levels of sitosterol and other plant sterols. The trafficking of cholesterol is also impaired leading to elevated plasma levels of LDL cholesterol.Sitosterolemia
Elevated plasma levels of LDL cholesterol. Patients develop tendon xanthomas as well as premature atherosclerosis. They may have episodes of hemolysis due to incorporation of plant sterols in RBC membranes.Sitosterolemia
ABCA1 transporter deficiency Tangier Disease
In its absence, HDL is rapidly cleared from the circulation. Low plasma HDL-C levels (<5 mg/dL) and extremely low circulating levels of apoA-I.Tangier Disease
Cholesterol accumulation in the reticuloendothelial system, resulting in hepatosplenomegaly and pathognomonic enlarged, grayish yellow or orange tonsils. The disease is associated with increased risk of premature atherosclerotic disease.Tangier Disease
Accumulation of Gangliosides GM2. Rapid, progressive and fatal neurodegenerative, blindness, cherry red macula, muscular weakness, seizures.Tay-Sachs Disease
Hexosaminidase A deficiencyTay-Sachs Disease
Decreased biogenesis of plasmalogens (one of the membrane phospholipids) and bile acids are decreased Zellweger Syndrome
Mutations in PEX genes that encode peroxins Zellweger Syndrome
Accumulation of very long chain fatty acids (VLCFA) and branched chain fatty acids (BCFA) Zellweger Syndrome
A patient presents with failure to thrive, displays hepatomegaly, high levels of iron and copper in the blood, and vision problems.Zellweger Syndrome