Clinical disorders of lipid metabolism

Published on 01/03/2015 by admin

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Clinical disorders of lipid metabolism

Lipoprotein disorders are some of the commonest metabolic diseases seen in clinical practice. They may present with their various sequelae which include:

coronary heart disease (CHD)

acute pancreatitis

failure to thrive and weakness

Classification

Currently there is no satisfactory comprehensive classification of lipoprotein disorders. Genetic classifications have been attempted but are becoming increasingly complex as different mutations are discovered (Table 67.1). Familial hypercholesterolaemia (FH), which may present with xanthelasma (Fig 67.1), tendon xanthomas, severe hypercholesterolaemia and premature coronary heart disease, may be due to any of over 500 different mutations of the LDL receptor gene. Mutations of the apolipoprotein (apo) B gene can give an identical syndrome. Familial hyperchylomicronaemia, which presents with recurrent abdominal pain and pancreatitis, may result from genetic mutations of the lipoprotein lipase or apo C-II genes. Eruptive xanthomas (Fig 67.2) are characteristic of hypertriglyceridaemia.

Table 67.1

Some genetic causes of dyslipidaemia

Fig 67.1 Xanthelasmas in younger individuals (age <40 years) usually indicate hypercholesterolaemia. In the elderly they do not carry the same significance.

Fig 67.2 Eruptive xanthomas in a patient with hypertriglyceridaemia.

Until gene therapy and/or specific substitution therapy become more widely available, genetic classifications, while biologically illuminating, are unlikely to prove very useful in practice. In practice, lipoprotein disorders are simplistically classified as being:

Primary – when the disorder is not due to an identifiable underlying disease.

Secondary – when the disorder is a manifestation of some other disease.

Primary

The Fredrickson or World Health Organization classification is the most widely accepted for the primary hyperlipidaemias (Fig 67.3). It relies on the findings of plasma analysis, rather than genetics. As a result, patients with the same genetic defect may fall into different groups, or may change grouping as the disease progresses or is treated (Table 67.1). The major advantage of this classification is that it is widely accepted and gives some guidance for treatment.

Fig 67.3 Fredrickson (WHO) classification of dyslipidaemia. This is based on the appearance of a fasting plasma sample after standing for 12 hours at 4°C and analysis of its cholesterol and triglyceride content.

The six types of hyperlipoproteinaemia defined in the Fredrickson classification are not equally common. Types I and V are rare, while types IIa, IIb and IV are very common. Type III hyperlipoproteinaemia, also known as familial dysbetalipoproteinaemia, is intermediate in frequency, occurring in about 1/5000 of the population.

Secondary

Secondary hyperlipidaemia is a well-recognized feature of a number of diseases (Table 67.2) that divide broadly into two categories:

Table 67.2

Common causes of secondary hyperlipidaemia

Disease	Usual dominant lipid abnormality
Diabetes mellitus	Increased triglyceride
Alcohol excess	Increased triglyceride
Chronic renal failure	Increased triglyceride
Drugs, e.g. thiazide diuretics	Increased triglyceride
Hypothyroidism	Increased cholesterol
Nephrotic syndrome	Increased cholesterol

Clinically obvious diseases such as renal failure, nephrotic syndrome and cirrhosis of the liver.

Covert conditions that may present as hyperlipidaemia. These include hypothyroidism, diabetes mellitus and alcohol abuse.

Atherogenic profiles

The causal association of certain forms of hyperlipidaemia and CHD is clearly the major stimulus for the measurement of plasma lipids and lipoproteins in clinical practice. The most common lipid disorder linked with atherogenesis and an increased risk of CHD is an elevated plasma LDL cholesterol level, but increasingly it is being recognized that individuals with low plasma HDL cholesterol and hypertriglyceridaemia are also at increased risk.

Clinical note

The physical signs of the hyperlipidaemias are not specific for any particular disease and may sometimes be present in normolipidaemic patients, e.g. arcus senilis (Fig 67.4). Their presence is, however, highly suggestive of raised lipids. Tendon xanthomas (Fig 67.5) are particularly associated with familial hypercholesterolaemia.

Fig 67.4 Arcus senilis.

Fig 67.5 Tendon xanthomas. These are pathognomonic for familial hypercholesterolaemia and are often first seen on the Achilles tendon as in this patient.

Case history 54

A 53-year-old man was found to have the following results on a fasting blood sample:

A non-smoker, his blood pressure was 145/95 mmHg and he was obese with central fat distribution.

• What other information and investigations would be helpful in this man’s management?

• What treatment options would you consider in this case?

Comment on page 169.

Clinical disorders of lipid metabolism

The Fredrickson classification is still commonly used to classify hyperlipoproteinaemias by phenotype.

The genetic and environmental nature of many causes of primary hyperlipidaemia are, as yet, unknown.

Secondary causes of hyperlipidaemia are common and include hypothyroidism, diabetes mellitus, liver disease and alcohol abuse.

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