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)
