Diseases and Drugs Flashcards
1
Q
- autosomal recessive
- loss of function mutation in gene encoding microsomal triacylglycerol transfer protein (MTP)
- chylomicrons, VLDLs, LDLs and apoB are undetectable in plasma leading to lipid malabsorption
- extremely low plasma levels of cholesterol and TAG
- Symptoms: early childhood, diarrhea, failure to thrive, deficient of fat soluble vitamins, spinocerebellar degeneration, pigmented retinopathy, acanthocytosis
A
Abetalipoproteinemia
2
Q
- Deficiency of LPL, abnormal LPL, or apo C-II deficiency
- slow clearance of chylomicrons and VLDL
- fasting plasma is turbid and develops creamy supernatant at 4*C
- Symptoms: manifests in childhood, recurrent episodes of severe abdominal pain due to acute pancreatitis, lipemia retinalis, eruptive xanthomas, hepatosplenomegaly
A
Familial Lipoprotein Lipase (LPL) Deficiency
3
Q
- autosomal recessive
- mutation in ATP-binding cassette (ABC) transporter family [ABCG5 and ABCG8]
- due to increased absorption of plant sterols in intestine and reduced transport of sterols into bile by liver
- impaired cholesterol trafficking
- elevated levels of LDL cholesterol
- Symptoms: tendon xanthomas, premature atherosclerosis
- episodes of hemolysis due to incorporation of plant sterols in RBC membranes
A
Sistosterolemia
4
Q
- autosomal codominant
- mutations in LDL receptor gene, mostly in ligand binding region on exon 4
- high LDL-C levels (200-400 mg/dL in heterozygotes, > 500 mg/dL in homozygotes)
- Symptoms: cutaneous xanthomas, accelerated atherosclerosis, corneal arcus, tendon xanthomas
- High incidence in Afrikaners, Christian Lebanese, and French Canadians
A
Familial Hypercholesterolemia (FH)
5
Q
- autosomal codominant
- due to mutation in gene encoding ABCA1
- HDL is rapidly cleared from circulation
- Low plasma HDL-C levels (
A
Tangier Disease (ABCA1 Deficiency)
6
Q
- autosomal recessive
- mutation in gene encoding plasma enzyme LCAT
- increased level of free cholesterol in lipoproteins (from 25% to 70% of total plasma C)
- lack of normal cholesterol esterification
- impairs formation of mature HDL
- low plasma concentraions of CE and lysolecithin, abnormal LDL and VLDL in circulation
- Symptom: progressive corneal opacification, variable hypertriglyceridemia
A
Familial Lecithin Cholesterol Acyltransferase (LCAT) Deficiency
7
Q
- autosomal recessive
- impairs oxidation of medium chain fatty acids (C8-C12)
- accumulation of medium chain fatty acids and esters in tissues
- spillover of C8-C12 acylcarnitine species in blood
- hypoglycemia during fasting due to lack of ATPs
- decreased gluconeogenesis and ketone body formation
- non-ketotic hypoglycemia and block in hepatic beta-oxidation
- lethargy, coma, and death if untreated
- treated by IV glucose, prevented with frequent feeding, high carb, low fat diet
A
MCAD Deficiency
8
Q
- inherited (autosomal recessive) or acquired
- mutation in genes for Carnitine Palmitoyl Transferase I or II
- low protein diet, impaired synthesis of carnitine in liver disease, loss of carnitine during hemodialysis process
- decreased LCFA metabolism leads to accumulation of LCFAs in tissues and wasting of acyl-carnitine in urine
- Symptoms: cardiomyopathy, skeletal muscle myopathy, encephalopathy, impaired liver function, muscle ache and weakness, rhabdomyolysis and myoglobinuria upon exercise
- treated with IV glucose and cease of muscle activity
A
Carnitine Deficiency
9
Q
- autosomal recessive
- mutation in PEX genes encoding for peroxins
- accumulation of VLCFAs and BCFAs that are normally degraded in peroxisomes
- Symptoms: liver and kidney dysfunction, hepatomegaly, high levels of copper and iron in blood, severe neurologic defects, hypomyelination, craniofacial and skeletal malformations
A
Zellweger Syndrome
10
Q
- autosomal recessive
- deficiency of peroxisomal phytanic acidhydroxylase
- impaired-oxidation of phytanic acid
- buildup of phytanic acid and derivatives in plasma and tissues
- cerebellar ataxia, retinitis pigmentosa, chronic polyneuropathy
- treated with low-phytanic acid diet
A
Refsum Disease
11
Q
- caused by ingestion of unripe Ackee fruit which contains hypoglycin A
- hypoglycin A is metabolized to methylenecyclopropylacetic acid (MCPA)
- MCPA interferes with transport of LCFAs into mitochondria and inhibits acyl-CoA dehydrogenases involved in beta-oxidation
- decrease in ATPs and gluconeogenesis
- severe vomiting 2-6 hours after ingestion, severe hypoglycemia, convulsions, coma, death
A
Jamaican Vomiting Sickness
12
Q
- low insulin/glucagon ratio stimulates excess beta-oxidation depleting NAD+ and saturating TCA cycle with acetyl CoA shunting acetyl CoA toward ketone body formation
- acetoacetic acid and 3-hydroxybutyric acid (ketone bodies) accumulate in blood and decrease pH
- acetone is volatile and hence exhaled giving fruit odor to breath
A
Diabetic Ketoacidosis
13
Q
- autosomal recessive
- Defective Hexosaminidase A by mutation in HexA gene
- accumulation of ganglioside GM2
- common in Ashkenazi Jews
- progressive destruction of nerve cells in the brain and spinal cord, muscle atrophy, cherry red spot in retinoscopy, blind, deaf, unable to swallow
A
Tay-Sachs Disease
14
Q
- X-linked recessive
- deficiency of alpha-Galactosidase
- accumulation of globotriaosylceramide/ceramide trihexoside
- skin rash (angiokeratomas), kidney failure, cardiac complications, hypertension, cardiomyopathy
- Fabry crises: episodes of intesnse, excruciating burning pain felt initially in hands and feet, radiating to other parts of the body
A
Fabry’s Disease
15
Q
- autosomal recessive
- deficiency of glucocerebrosidase (beta-glucosidase)
- accumulation of glucocerebrosides in WBC, spleen, liver, kidney, lung, brain and bone marrow
- hepatosplenomegaly, anemia, thrombocytopenia, leukopenia, easily bruised, convulsions, hypertonia, dementia, ocular muscle apraxia
- “wrinkled tissue paper” looking cytoplasm of gaucher cells
A
Gaucher’s Disease
16
Q
- autosomal recessive
- complete absence of sphingomyelinase enzyme
- accumulation of sphingomyelin
- hepatosplenomegaly, ataxia, dusarthria, dysphagia, dystonia, supranuclear gaze palsy, dementia, seizures, cherry red spot retinoscopy, foam cells
A
Niemann-Pick Disease
17
Q
- autosomal recessive
- deficiency of ceramidase
- accumulation of ceramide in joints, CNS, throat, liver and other tissues
- subcutaneous nodules, tissue granulomas, joint pain, joint swelling, hoarseness of voice
A
Sandhoff Disease
18
Q
- defective or absence of Sandhoff activator protein (required by hexosaminidase A)
- accumulation of GM2 ganglioside
- mental retardation, blindness, muscular weakness
A
Sandhoff Activator Disease
19
Q
- autosomal recessive
defect in intestinal absorption and kidney reabsorption of neutral amino acids - niacin deficiency and pellagra
A
Hartnup Disease
20
Q
- defect in the transportof cysteine and basic amino acids (arginine, lysine, ornithine) across both intestinal and renal epithelial cells
- insolubility of cysteine forming kidney stone
A
Cystinuria
21
Q
- inflammation and ischemia of pancreatic tissue to acinar cell damage
- abnormal activation of trypsin inside acinar cells activating other proteolytic enzymes leading to self sustaining cycle of digestion of pancreatic tissues
A
Acute Necrotizing Pancreatitis
22
Q
- autosomal recessive
- defective PAH gene
- accumulation of phenylalanine in the blood
- gradual development of irreversible mental retardation if not diagnosed within first month of life
- albinism, must or mousy odor of sweat and urine
- treated by phenylalanine restricted diet and avoidance of aspartame
- tyrosine becomes essential to diet
- congenital heart disease, growth retardation, microcephaly, and mental retardation in babies born to PKU mothers
A
Classic Phenylketonuria (PKU)
23
Q
- defective dihydropteridine reductase (DHPR) so there is normal quantity of PAH, but decreased activity
- deficiency of BH4
- albinism, must or mousy odor of sweat and urine
- progressive neurological manifestation and eventual death
A
Non-Classical Phenylketonuria (PKU)
24
Q
drug that is a synthetic form of BH4 that stimulates the activity of the residual PAH enzyme in PKU patients
A
KUVAN
25
- genetic defect in
- encoded by gene TAT
- leasions of the eye and skin, neurological problems
- treated with low tyrosine and phenylalanine diet
Hereditary Tyrosinemia Type 2
26
- deficiency of the enzyme 4-hydroxyphenlpyruvate dioxygenase
- encoded by gene HPD
- common in premature newborns
Hereditary Tyrosinemia Type 3
27
- deficiency of fumarylacetoacetate hydrolase
- most severe form of disease
- liver failure, cabbage like body odor, death within first year of life
Hereditary Tyrosinemia Type 1
28
- autosomal recessive
- deficiency of homogentisic acid 1,2 dioxygenase (homogentisic acid oxidase)
- accumulation of homogentisic acid in body fluids and is autooxidized to quinone form
- quinone form accumulats over cartilage
- ochronosis [deposition of oxidized pigments]
- dark urine, gray-brown scleral pigment, low back pain, bamboo spine
Alkaptonuria /black urine disease
29
- commonly because of deficiency or defect in
| - generalized hypopigmentation, photophobia, photosensitivity, higher susceptibility for skin cancer
Albinism
30
ingestion of food with high tyramine content along with MAO inhibitors will cause elevated tyramine levels thus releasing NE leading to sympathomimetic effects
The Cheese Effect
31
drug that was originally designed for treatment of TB but has shown mood swings due to MAO inhibitory effects and has cheese effect
Iproniazid
32
MAO-A inhbitor used for clinical depression has shown cheese effect
Clorgyline
33
MAO-B inhibitor used in treatment of Parkinson's disease that decreases dopamine catabolism and increases dopmaine levels. does not show cheese effect
Deprenyl
34
reversible MAO-A inhbitor which is used in clinical depression and does not show cheese effect. increases serotonin levels within a certain range of tyramine levels until tyramine displaces the drug. no cheese effect
Moclobemide
35
- tumor of neuroendocrine system of the GI tract
- flushing and diarrhea
- elevated plasma serotonin or elevated urinary 5-HIAA
Carcinoid Syndrome
36
- autoimmune neuromuscular disease
- inhibition of acetycholine on nicotinic receptors at
- treated with acetylcholinesterase inhibitors, immunosuppressants, and thymectomy
Myasthenia Gravis
37
drug that inhibits the reuptake of GABA from synapse and used as anticonvulsant
Tiagabine
38
- reduced activity of cystathionine B-synthase, Cystathionase, or deficiency of vitamin B6
- excessive blood clotting, similar signs of Marfan syndrome, osteoporosis, mental retardation, retinal damage, lens dislocation in inferomedial direction
- accumulation of homocysteine and methionine
Classic Homocysteinuria
39
- impaired remethylation of homocysteine to methionine
- deficiency or defect in: methyl-B12, N5N10 methylene THF, methionine synthase, N5-methyl THF, N5N10-methylene THF reductase
- excessive blood clotting, similar signs of Marfan syndrome, osteoporosis, mental retardation, retinal damage, lens dislocation in inferomedial direction
- accumulation of homocysteine
Non-Classic Homocysteinuria
40
- autosomal recessive
- defect in branched chain alpha-keto acid dehydrogenase
- build up of leucine, isoleuicine, and valine and their byproducts in blood and urine
- urine has maple syrup or burnt sugar odor
- severe brain damage and death if untreated from birth
- poor feeding,vomiting, dehydration, lethargy, hyoptonia, seizures, ketoacidosis, coma
Maple Syrup Urine Disease
41
- overproducation hyperuricemia
- defect in hypoxanthine-guanine phosphoribosyl transferase (HGPRT)
- self-mutilation, decreased IQ, uric acid lithiasis, uric acid crystals (orange sand) in urine
Lesch-Nyhan Syndrome
42
- autosomal recessive
- mutation in ADA gene coding for adenosine deaminase
- cause for about half of cases of SCID
- accumulation of dATP inhibiting ribonucleotide reductase leading to deficiency of other deoxyribonucleotides
- dysfunctional and sparse B cells and T cells
Adenosine Deaminase (ADA) Deficiency
43
- defect or deficiency of both orotate phosphoribosyltransferase and orotidylate decarboxylase
- megaloblastic anemia with no response to vitamin B12
- orotate in urine
Type I Orotic Aciduria
44
- x linked recessive
- most common urea cycle defect
- elevated levels of ammonia and glutamine leads to neurotoxic effects
- mental retardation and elevated levels of orotic acid
Ornithine Transcarbamylase (OTC) Deficiency
45
drug that readily crosses the blood brain barrier and is rapidly decarboxylated to serotonin. Often used in the treatment of depression and epilepsy
5-HT
46
ribonucleotide reductase inhibitor used in myeloproliferative disorders
Hydroxyurea
47
inhibitor of thioredoxin reductase and ribonucleotide reductase
Motexafin gadolinium
48
nucleoside analogue and irreversibly inhibits ribonucleotide reductase
Gemcitabine
49
inhibits xanthine oxidase and hence decreases uric acid formation
Allopurinol
50
- purine overproduction and hyperuricemia occurs secondary to enhanced generation of the PRPP precursor ribose 5-phosphate
- lactic acidosis elevates the renal threshold for urate
Von Gierke Disease
51
- autosomal recessive cause: mutation in ADA gene, IL-7 receptor alpha gene and RAG-1 and RAG-2 genes
- x-linked inheritance pattern: defective gene coding for gamma chain of the receptors for IL-2, 4, 7, 9, 15
SCID
52
deficiency of only orotidylate decarboxylase
type II orotic aciduria
53
neurological symptpms
cobalamin deficiency
54
no newurological problems
folate deficiency
55
doesn't respond to colbalamin, folate, B6, or iron supplementation, but does to uridine
orotic aciduria
