diagnosis and investigation

Last edited 07/2019

• cholesterol and triglycerides - fasting levels of cholesterol and triglycerides are raised (generally cholesterol 7-12 mmol/L and triglycerides 5-20 mmol/L); often the molar concentrations of cholesterol and triglycerides are similar in type IIb hyperlipidaemia; there may occasionally be a severe hypertriglyceridaemia because of a massive, overwhelming chylomicronaemia
• clinical features:
  • xanthomata - present in about 50% of patients with type III hyperlipoproteinaemia; characteristically striate palmar xanthomata (may be an orange discoloration of skin creases or may be raised papules in the skin creases of the palms, fingers and flexor surfaces of the wrists) and tuberoeruptive xanthomata (often occur over the elbows and knees); resolve completely if successful treatment
• laboratory investigations include:
  • if typical xanthomata are present together with associated levels of cholesterol and triglyceride - further laboratory tests are generally not required for the diagnosis
  • if absent xanthoma then hyperlipoproteinaemia with similar levels of cholesterol and triglyceride can occur in type IIb or V hyperlipidaemia
    • lipoprotein electrophoresis - may be available - useful in differentiating type IIB from type III hyperlipidaemia if can show seperate pre-ß VLDL and ß LDL bands
    • DNA testing by restriction-fragment-length polymorphism - may be used to identify Apo E2 homozygosity - note that testing for apo E genotype may reveal apo E4 is present (has been linked to the development of Alzheimer's disease); therefore it is important to specify testing specifically as to whether apo E2 homozygosity is present or not so further information about apo E genotype is not entered into the patient's medical record
    • ultracentrifugation - may identify cholesterol-rich VLDL (ß - VLDL) which is characteristic of type III hyperlipidaemia
    • immunoglobulin electrophoresis to exclude paraproteinaemia - this may result in a hyperlipidaemia which is similar to a type III hyperlipoproteinaemia