Familial Hyperlipidemias

Type I

{Familial LPL deficiency
Familial hyperchylomicronemia}

↓ Lipoprotein lipase (LPL) or apoprotein CII defect

↑↑ TG
(chylomicrons)

Eruptive xanthomas, acute pancreatitis abdominal pain, lipemia retinalis

Type IIa

{Familial hypercholesterolemia
Familial defective apo B100}

LDL receptor defect (mutation of LDLR or apo B)

Yes

Clear

↑↑ Cholesterol
(LDL)

Tendinous and tuberous xanthomas, xanthelasma

Type IIb

{Familial combined hypercholesterolemia}

LDL receptor
defect

Yes

Clear or
cloudy

↑ Cholesterol
↑ TG
(LDL, VLDL)

Tendinous and tuberous xanthomas, xanthelasma

Type III

{Familial dysbetalipoproteinemia}

Apoprotein E
defect

Yes

Turbid

↑ Cholesterol
↑ TG
(IDL, VLDL)

Xanthoma striatum palmare,
{pathognomonic}

tuberous xanthomas

Type IV

{Familial hypertriglyceridemia}

↑ Production
of VLDL

±

Turbid

↑ TG
(VLDL, IDL)

Apolipoprotein
C-II defect

±

Creamy
top layer

↑↑ TG
↑ Cholesterol
(VLDL, chylo)

Tuberous xanthomas
(seen in type II, III)

Pink-yellow papulonodules on extensor pressure surfaces, especially knees/elbows; slow to regress after initiation of treatment; seen in hypercholesterolemic states

Tendinous xanthomas
(II, III)

Smooth nodular lipid deposits of the Achilles tendon > extensor tendons of hands, knees or elbows; may also see in hepatic cholestasis secondary to primary biliary cirrhosis

Plane xanthomas
(II, III)

Yellow slightly elevated plaques typically involving eyelids, trunk, neck, shoulder or axillae; may also be from biliary cirrhosis; if normolipemic, may be associated with monoclonal gammopathy (IgG)

{Intertriginous almost pathognomonic for homozygous familial hypercholesterolemia}

Xanthoma striatum
palmare (III)

Type of plane xanthoma over palm with yelloworange infiltration of volar creases (palms and fingers), characteristic for type III

Xanthelasma
(II, III)

Plane xanthoma of eyelid; yellow flat-topped papules or plaques around medial eyelids; only half of patients with hyperlipidemia

Eruptive xanthomas
(I, IV, V)

{Do not confuse with xanthoma disseminatum}

Eruption of small yellow papules with erythematous base on back, buttocks, chest, and proximal extremities; seen in hypertriglyceridemic state (often >3,000 mg/dl); associated with diabetes, pancreatitis, chronic renal failure

Xanthoma disseminatum: occurs in normolipemic patients; red-yellow papules with flexural predilection