Makindo Medical Notes

In familial lipoprotein lipase deficiency, the blood can appear milky due to its high fat content, primarily caused by elevated levels of chylomicrons.

About

• Lipoprotein Lipase Deficiency: A rare genetic disorder in which lipoprotein lipase (LPL), an enzyme essential for the hydrolysis of triglycerides in lipoproteins, is deficient or absent.
• Lipoprotein lipase is produced by many tissues, including adipose tissue, skeletal muscle, and the heart.
• It is the rate-limiting enzyme for the removal of triglycerides from circulating lipoproteins, primarily chylomicrons and very-low-density lipoproteins (VLDLs).
• This deficiency results in a high level of chylomicrons in the blood, leading to severe hypertriglyceridemia.

Aetiology

• Autosomal recessive disorder.
• Caused by mutations in the LPL gene, which encodes the lipoprotein lipase enzyme.

Clinical Features

• Pancreatitis: Recurrent episodes of acute pancreatitis due to elevated triglyceride levels are common.
• Hepatosplenomegaly: Enlargement of the liver and spleen due to fat accumulation.
• Eruptive Xanthomas: Yellowish, small bumps (xanthomas) may appear on the skin, particularly on the trunk, buttocks, knees, and arms.
• Retinal Manifestations: Lipemia retinalis (milky appearance of retinal vessels) and an increased risk of retinal vein thrombosis due to high triglyceride levels.
• Potentially increased risk of cardiovascular disease or diabetes in later life, although these associations may vary.

Differentials

• Other causes of hypertriglyceridemia, such as familial combined hyperlipidemia or familial hyperchylomicronemia syndrome.
• Hyperlipidemia secondary to uncontrolled diabetes or hypothyroidism.
• Drug-induced hypertriglyceridemia (e.g., due to corticosteroids or estrogens).

Investigations

• Blood tests show elevated levels of chylomicrons and marked hypertriglyceridemia.
• Triglyceride levels are typically >10 mmol/L (880 mg/dL), and in some cases, much higher.
• Lipoprotein electrophoresis or ultracentrifugation can confirm the presence of chylomicrons.
• Genetic testing can confirm mutations in the LPL gene.

Management

• Low-fat diet: Reducing dietary intake of long-chain triglycerides is key. A very low-fat diet helps minimize the accumulation of chylomicrons in the blood.
• Medium-chain triglycerides (MCTs): These can be used as an alternative source of fat, as they are absorbed directly into the bloodstream without the need for LPL.
• Avoidance of alcohol: Alcohol can exacerbate hypertriglyceridemia and increase the risk of pancreatitis.
• If triglyceride levels are between 2.0 and 6.0 mmol/L, management may involve general cardiovascular risk reduction.
• For triglyceride levels >6.0 mmol/L, the risk of pancreatitis and retinal vein thrombosis increases significantly, and more aggressive management is required.
• Fibrates or Omega-3 fatty acids: These may be considered to help lower triglyceride levels, but their use in LPL deficiency is limited.

References