31 terms

Laboratory Diagnosis 3.1.2: Lipids and Lipoprotein diseases

STUDY
PLAY

Terms in this set (...)

origin
electrophoretic mobility:
chylomicrons
pre-beta
electrophoretic mobility:
VLDL
broad beta
electrophoretic mobility:
IDL
beta
electrophoretic mobility:
LDL
alpha
electrophoretic mobility:
HDL
HIGH CHOLESTEROL WITH HIGH LDL-C
- main feature is hyperbetalipoproteinemia
- Fredrickson Classification type 2A
- elevated LDL-C
- normal triglyceride
Polygenic Hypercholesterolemia
- nonfamilial
- cause is multifactorial
- cause could be genetic
- increase in cholesterol due to age related cause do not respond to lifestyle changes
familial hypercholesterolemia (FC)
- autosomal dominant disorder
- mutations in the LDL receptor gene on chromosome 19
- defective receptors cannot bind or clear LDL from the circulation
Heterozygous FH
- associated with atherosclerotic disease
- affects men: 40 y/o and women: 50-55 y/o
- LDL-C levels are 220mg/dL
- LDL-C levels are affected by environmental factors and genetics
- adulthood presents with corneal arcus, tendinous xanthomas, and xanthelasma


treatment: STATINS
Homozygous FH
- present in childhood
- LDL levels of 400 mg/dL
- premature symptomatic CHD
- LDL-C levels less affected by env'tal factors
- symptomatic aortic stenosis due to valvular and supravalvular cholesterol deposits
- childhood presents with corneal arcus, tendinous xanthomas, and xanthelasma

treatment:
STATINS + APHERESIS
receptor-negative
HomoFH LDL receptor:

- less than 2% normal LDLR activity
- pts rarely live past the 2nd decade
receptor-defective
HomoFH LDL receptor:

- 2 -25% normal LDLR activity
- atherosclerotic disease by the age of 30
Familial defective ApoB
- autosomal dominant disorder on chromosome 2
- missense mutation (Arg3500Gln) in the LDLR binding domain of apoB-100
- present with tendinous xanthomata, xanthelasma, premature plasma LDL-C

treatment: STATIN
Sitosterolemia
- autosomal recessive disorder
- phytosterols are absorbed and accumulate in plasma and peripheral tissues
- mutations in the ABCG5 or ABCG8 gene at chromosome 2p2 (disrupt formation of proper channel for phytosterol absorption)
- high LDL-C levels during childhood
- present with low-level hemolysis
- present with xanthomatosis and hypercholesterolemia but parents have normal cholesterol levels

treatment:
- restrict phytosterols
- EZETIMIBE and BILE ACID SEQUESTRATION
autosomal dominant hypercholesterolemia (ADH)
- autosomal dominant disorder of PCSK9 gene on chromosome 1 (cholesterol homeostasis in the liver)
- mutations of S127R and F216L lead to gain of function of PCSK9 resulting to endocytosis and intracellular degradation of LDLR
- missense (R46L) and nonsense (Y142X and C697X) mutations lead to HYPOcholesterolemia
HIGH TRIGLYCERIDES WITH NORMAL CHOLESTEROL
- d/o related to elevations of CM or VLDL
- Fredrickson types 1 and 4
- hyperPREBETAlipoprotenemia (VLDL)
- 2ndary causes are alcohol and high carbohydrate diet
diabetic dyslipidemia
- atherogenic dyslipidemia with high triglycerides and low HDL in persons with DM2
- cholesterol levels within normal
Familial hypertriglyceridemia
- part of hyperlipidemia syndromes
- isolated hypertriglyceridemia or type 4 hyperlipidemia
- autosomal dominant disorder
- resents in adulthood with fasting TG 200-250mg/dL
- fluffy, TG-rich VLDL
- have premature CHD
Lipoprotein lipase deficieny
- aka: hyperLIPOPROTEINemia type 1 or hyperCHYLOMICRONemia
- autosomal recessive disorder
- present in childhood with abdominal pain and pancreatitis
- absent LPL lead to inability to clear chylomicron
- non-atherogenic
ApoC-II deficiency
- deficiency of the activating cofactor for LPL
- presents similarly to LPL deficiency

treatment:
- plasma transfusion
- providing apoC-II
ApoC-III excess
- interferes with the activity of LPL
- competitively binds to the carboxy-terminal portion of apoB
- prevention of LDL and VLDL binding to the LDLR may be a risk factor for CHD
- present in diabetics and diabetics with hypertriglyceridemia
HIGH cholesterol with HIGH triglyceride
- d/o related to elevation of LDL and TG
- Fredrickson types 2B and 3
Familial combined hyperLIPIDemia (Type 2B)
- most common hyperLIPOPROTEINemia
- common d/o
- affected individual may have simple hyperCHOLESTEROLemia, simple hyperTRIGLYCERIDemia, or a mixed defect
- initially thought to be autosomal codominant
Acquired combined hyperLIPIDemia
- common in patients who have metabolic syndromes:
- DM2
- HPN
- central obesity
- CHD
- liver increases production of VLDL
- VLDL matures to LDL
- certain increase in LDL causes VLDL increase leading to hyperCHOLESTEROLemia and hyperTRIGLYCERIDEmia respectively
dys beta lipoprotein emia (Type 3)
- increased lipoprotein in the circulation because of homozygous apoE-2 that has lower affinity for the LDL receptor
- pathognomonic feature: broad abnormal band between VLDL and LDL known as 'abnormally migrating beta lipoprotein' or 'B-VLDL'
- cholesterol content in VLDL is increased

treatment: low fat diets, weight loss, lipid lowering drugs
ApoE-3
most common isoform of apoE (binds to LDL receptor)
Hepatic Lipase deficeincy (HDL)
- results from mutations of the Hepatic Lipase gene
- TC 250-1500 mg/dL and TG 400-8000 mg/dL >>>>> combined hyperlipidemia
- triglyceride CONTENT of all lipoproteins is increased 3-fold to 5-fold
- unable to convert VLDL to IDL then to LDL
Cholesterol 7-Alpha-Hydroxylase Deficiency
- recessive d/o of the CYP7A1 gene
- pts present with high cholesterol and high triglyceride
- resistant to statin therapy
- plasma cholesterol is lowered with ATORVASTATIN and NIACIN therapy
CYP7A1 gene
encodes an enzyme that is involved in the first step of the classical pathway for the bile acid biosynthesis
LOW TC and TG
- associated with defective apo-B synthesis or metabolism
- low or non-existent CM, VLDL and LDL
- fat-soluble vitamin deficiencies are common
- low fat diet therapy
A beta lipoprotein emia (Bassen-Kornzweig syndrome)
...