Ans. is 'b' i.e., Type II hyperlipidemia FRADERICKSON CLASSIFICATION OF HYPERLIPIDEIVRA 1. Type Ilfamilial lipoprein lipase deficiency) o Lipoprotein lipase is required for the hydrolysis of chylomicrons and VLDL tri glycerides. o Deficiency of LPL results in decrease hydrolysis and elevated levels of plasma chylomicrons. o VLDL may also be increased but chylomicrons predominate. o Clinical manifestations Severe abdominal pain due to acute pancreatitis. Lipemia retinalis --> opalescent retinal vessels. Eruptive xanthomas ---> on back, buttocks and extensor surface of legs and arms. Hepatosplenomegaly --> due to uptake of chylomicron by RE cells of liver & spleen. Note - Similar disorder may occur with Apo-C II deficiency, because apo C-II acts as a cofacter for LPL (see previous explanations on lipid transpo). In Apo II deficiency, LPL becomes inactive. 2. Type II A.Tvpe Ha (familial hvpercholesterolemia) o It is due to deficiency of LDL receptors. o There are two sources of increased LDL Decreased clearance of LDL LDL receptors. Increased production LDL from IDL normally 40-60% of IDL is taken up by liver LDL receptors, but in LDL receptor deficiency, clearance of IDL is decreased. So, more IDL is conveed to LDL. o Clinical manifestations Tuberous and tendon xanthoma on hands, wrist, elbows, knees, heels (especially the achilles tendon) or buttocks. Xanthelesma --> Barely elevated deposits of cholesterol over eyelids. Premature atherosclerosis coronary hea diseases. Peripheral vascular disease Corneal arcus B.TypeIlb (familial combined hvperlipidemia) o It is a disorder genetically distinct from the other inherited hyperlipidemias and characterized by the type II or type IV lipoprotein pattern that may change from time to time. o It is due to L LDL receptors and increased secretion of Apo B-100 (major apoprotein of VLDL) -9 So, both LDL and VLDL are increased. o Clinical manifestations There are no xanthomas (as seen with type 11a). Increased risk of CHD. Peripheral vascular disease. 3. Type DI (Familial dysbetalipoproteinemia) o Also known as familial broad - $ disease. o This is due do abnormality in Apo - E. o Apo - E acts as a ligand for LDL receptors and helps in hepatic uptake of chylomiron remnants and VLDL remnants, i.e. IDL (see previous explanations of lipid transpo). o Due to defective uptake, Chylomicron remnants and VLDL remnants (IDL) are increased. o Clinical manifestations Tubero-eruptive xanthomas. Palmar xanthomas (xanthomata striata palmas). Premature atherosclerosis --* CHD Peripheral vascular disease Type IV (familial hyperiglyceridemia) o There is elevated levels of VLDL due to increased hepatic production of VLDL and impaired catabolism of VLDL. o It may be due to Apo - V deficiency (Apo - V promotes LPL mediated triglyceride lipolysis). o Premature coronary aery disease may occur but the chances are very-very less than in type II & Type III hyperlipidemias. Type V (Endogenous hvperiglyceridemia) o Pathogenesis may be similar to type IV, but it is more severe and both VLDL and chylomicrons are raised because both these are metabolized by same LPL and competes with each other for metabolism. o Clinical manifestations These are same as in type I familial LPL deficiency, i.e. o Pancreatitis o Lipemia retinalis o Eruptive xanthomas o Hepatosplenomegaly