Dyslipidaemias

Polygenic forms: 1 in 20

Heterozygous form: 1 in 250

Mutations: PCSK9, LDLR, APOB genes (all cause reduction in receptor mediated clearance of LDL-C)

Lipid profile: elevated LDL-C, low-normal triglycerides, TC 9-12

Dx of heterozygous form: 

• 1: TC > 7.5 or LDL-C > 4.9
• 2: Tendon xanthomas in pt or in 1st/2nd degree relative
• 3: DNA evidence
• 4: Premature CHD in pt or 1st degree relative (<60) or 2nd degree relative (<50)
• 5: TC > 7.5 or LDL-C > 4.9 in 1st or 2nd degree relative

1 + (2 or 3) = definite FH. 1 + (4 or 5) = possible FH.

1 in 100. Mutation unknown, possibly multigenic.

Lipid profile: elevated LDL-C, TC 6.5-10, usually low HDL-C, often elevated triglycerides, non-HDL-C/ApoB ratio < 5, VLDL-C/triglycerides ratio < 0.69

Suspect in an individual with moderate-severe mixed hyperlipidaemia and a PMH/FH of hyperlipidaemia/premature CHD

Screened family members may have:

• isolated raised triglycerides +/- low HDL-C
• mixed hyperlipidaemia
• isolated elevated LDL-C
• HTN with hypercholesterolaemia (familial dyslipidaemic HTN)

1 in 5000.

Lipid profile: TC 8-16, TG 4.5-9, cholesterol enriched beta VLDL remnants present, non-HDL-C/ApoB ratio > 5, VLDL-C/triglycerides ratio > 0.69

Autosomal recessive with low penetrance

Striate palmar and tuberoeruptive xanthomas

Multigenic forms 1 in 300, other forms rarer and more severe.

Lipid profile: elevated triglycerides (mild = 2.3-10, severe > 10), usually normal ApoB, small dense LDL-C (pattern B on gradient gel), usually low HDL-C except in XS alcohol

Eruptive xanthomas, lipaemia retinalis in severe

Severe forms prone to pancreatitis, DM and metabolic syndrome