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Lipidology Group

Group members
Prof David Marais Principal Investigator
Gabi Solomon Scientific Officer
Bharati Ratanjee Medical Technologist
Dr Justine Cole PhD student

 

Definition

Lipidology is a fascinating discipline that integrates physical and organic chemistry, biochemistry, cell biology, genetics,  molecular biology, nutrition, physiology, pathology, pharmacology, medical practice and  epidemiology. Lipidology not only  covers the common multifactorial disorders such as atherosclerosis with the risk of coronary, cerebral and peripheral arterial disease but also includes many errors of metabolism in lipid and lipoprotein metabolism.

Lipidology involves clinical medicine at all levels of healthcare, metabolic expertise, diagnostic procedures, and therapy of biochemical disturbances as well as a broad range of research. Special interest fields are general medicine, general paediatrics, endocrinology, cardiology, metabolic medicine, imaging and pharmacology. Whilst lipidology relies mostly on routine laboratory investigations, special investigations are often required to describe specific lipids, lipoproteins and genetic problems. In this setting, Lipidology is an extension of inborn errors of metabolism which has a strong history in Chemical Pathology at UCT.
 

Lipidology at UCT

The interest in lipidology dates back to the 1950s with the description of coronary artery disease in the urbanising black population of Cape Town. The lipid clinic in Internal Medicine at Groote Schuur Hospital in the 1960s diagnosed disorders such as dysbetalipoproteinaemia and cerebrotendinous xanthomatosis. An excellent diagnostic laboratory was developed by Prof M Berger in Chemical Pathology at the Red Cross Children’s War Memorial Hospital in the 1970s and 1980s.  Much research was done on familial hypercholesterolaemia in the 1980s by Prof W Gevers in Medical Biochemistry when supported by the Medical Research Council of South Africa.  The current laboratory expertise was developed since the 1990s in Internal Medicine and merged with Chemical Pathology in 2012.

Lipidology expertise is shared between Clinical Lipidology in the Department of  Internal Medicine under the leadership of Prof Dirk Blom  and Laboratory Lipidology in Department of Pathology under the leadership of Prof David Marais.

Clinical Lipidology consultation for patients takes place at Groote Schuur Hospital as well as the Health Science Faculty of UCT. The contact person for appointments is Sister Jenny Ross-Barron at 021 4042265 (answering machine) and discussion about problems or for information may be undertaken with both specialists for clinical and laboratory problems. Clinical Lipidology performs pharmaceutical trials with new modalities of treatment for severe disorders.

Laboratory Lipidology is geared towards investigation severe and uncommon disorders of lipid and lipoprotein metabolism. There is scope to undertake spectrophotometric and fluorimetric assays, genetic tests, electrophoresis, thin layer chromatography, size exclusion chromatography and some gas and high performance liquid chromatography, and ultracentrifugation. A Direct Analysis in Real Time mass spectrometer is being developed for diagnosis of metabolic disorders.
 

Lipidology assistance

Lipidology is currently not emphasised in postgraduate training and assistance may be required in several clinical and laboratory settings. These are summarised as:


Hypercholesterolaemias
Total cholesterol (TC) > 7.5mmol/L. (Includes disorders of LDL, HDL and LpX in cholestasis). 
Low density lipoprotein cholesterol  (LDLC) > 5.0 mmol/L (often single gene disorder)
High density lipoprotein cholesterol (HDLC) >2.5mmol/L (may not protect against atherosclerosis)


Hypertriglyceridaemias
These should be evaluated in the fasting state and are much influenced by diabetes or control thereof. 
Triglyceridaemia (TG) > 5.0mmol/L. May need better therapeutic strategies.
Triglyceridaemia (TG) >15mmol/L. High risk of pancreatitis; requires urgent attention.

Hypolipidaemias

Usually low TC and TG occur together, commonly as an acute phase response to illness but in other settings clinical problems may occur with the following values:
TC <2 mmol/L
LDLC <1.0 mmol/L
HDLC <0.7mmol/L

Clinical Problems
1. Premature atherosclerosis in children or adolescents,  men before 45 years, women before 55 years. 
2. Xanthomata of the skin and/or tendons except for xanthelasma at the eyes. 
3. Intolerance or poor response to medication. 
4. Lipodystrophies. 
5. Uncertainty about diagnosis.

Metabolic Disorders of Interest
1. Affecting vascular system: hyperhomocysteinaemia (>30μmol/L), phytosterolaemia (sitosterolaemia)
2. Affecting the neuro-mucular system: abetalipoproteinaemia, adrenoleukodystrophy (very long chain fatty acids), beta-oxidation of fatty acids (hypoketotic hypoglycaemias),  cerebrotendinous xanthomatosis, Refsum’s disease (phytanic acid), 
3. Affecting sterol biosynthesis: Conradi-Hünermann syndrome (8 dehydrocholesterol),  desmosterolosis, lathosterolosis, mevalonic aciduria, Smith Lemli Opitz syndrome (7-dehydrocholesterol)
4. Affecting the skin: eruptive xanthomata, ichthyosis (cholesterol sulphatase deficiency)
5. Affecting bile acid metabolism: cerebrotendinous xanthomatosis, hypercholanaemia.
 

 

Special Tests Available at Lipidology Laboratory

The Lipidology Laboratory, previously supported by the Medical Research Council,  investigates severe  dyslipidaemias at a phenotypic and genotypic level with the methods enumerated above.  In principle, we are interested in assisting with unmet needs following clinical discussion. Some tests are available depending on costs and staff availability. A price list is being drawn up.

These tests are coded as Chemistry: [Ch], Electrophoresis [E], Genetic [G], Thin Layer Chromatography [T], Cell Culture [Ce]. Cell culture requires skin biopsy and takes a minimum of 6 weeks.

Test Requirement Comment
[Ch] Bile acids 1mL serum Can screen for cerebro-tendinous xanthomatosis
[Ch] 7-dehydrocholesterol concentration,
(Smith Lemli Opitz syndrome)
1mL EDTA plasma Weekly
Not quantitatively exact  but specific
[Ch] Lipase activity 2mL EDTA plasma before and after heparin injection  
[E] LDL particle size, LpX , dysbetalipoproteinaemia 1mL EDTA plasma Weekly
[G]  LDL Receptor
(heterozygous FH phenotype)
5mL EDTA blood Founder effects more cost-effective. Not always essential unless homozygous FH considerations.
[G] binding defective apoB
(heterozygous FH phenotype)
5mL EDTA blood Not always essential unless homozygous FH considerations.
[G] PCSK9
(heterozygous FH phenotype)
5mL EDTA blood Not always essential unless homozygous FH considerations.
[G] ApoE (dysbetalipoproteinaemia) 5mL EDTA blood Best to have phenotype support
[G] 7-dehydrocholesterol reductase
(Smith Lemli Opitz syndrome)
5mL EDTA blood Best to have phenotype support
[G] Lipoprotein lipase 5mL EDTA blood Best to have phenotype support
[T] Phytanic acid, Refsum disease 1mL EDTA plasma Qualitative test
[Ce] Establish a fibroblast line Skin biopsy  
[Ce] LDL uptake Skin biopsy
diI labelled LDL prepared in-house
work-up of homozygous FH phenotype
[Ce] Niemann-Pick C Skin biopsy
Filipin stain