Primary Hyperlipidemia

4. Primary Hyperlipidemia

Once it is verified that hyperlipidemia occurs after a 10- to 12-hour fast, and all possible causes of secondary hyperlipidemia have been ruled out, a presumptive diagnosis of primary hyperlipidemia is made. There is one well described heritable primary hyperlipidemia in cats. In humans, many different gene mutations or defects resulting in primary hyperlipidemias have been characterized. It is likely that with further study and characterization, additional defects causing primary hyperlipidemia will be identified in the cat.

An idiopathic familial hyperchylomicronemia was first reported in two cats in New Zealand (Jones et al., 1983). Since that time, inherited hyperchylomicronemia has been reported in cats in a number of countries including the USA (Bauer & Verlander, 1984; Grieshaber et al., 1991), France (Jones, 1993), and the UK (Watson et al., 1992). The fact that many of the cats in these initial studies were related, suggested an inherited condition.

Idiopathic familial hyperchylomicronemia is often recognized in kittens or young cats, and affects a number of different breeds.

The most common physical examination findings of inherited hyperchylomicronemia are xanthomata and lipemia retinalis (Table 4) (Jones, 1993)

Xanthomata are lipid deposits in skin and organs (Figure 9). Xanthomata are often present in peripheral nerves (Jones et al., 1986), and Horner’s syndrome, tibial nerve paralysis, and radial nerve paralysis are most common. Xanthomata can also occur in the liver, spleen, lymph nodes, kidney, heart, muscle, and intestines (Thompson et al., 1989; Johnstone et al., 1990; Grieshaber et al., 1991; Chanut et al., 2005). The histopathology of these lesions have been studied, and are characterized by abnormal lipid accumulation in tissues (Thompson et al., 1989).

Figure 9. Xanthomata in a hyperlipidemic cat. Xanthomata are often present in peripheral nerves and can cause a Horner's syndrome.

Lipemia retinalis occurs when hypertriglyceridemia is severe and greater than 15 mmol/L (1364 mg/dl). Lipid keratopathy (Carrington, 1983), lipid in the anterior chamber of the eye (Brooks, 1989), or lipid deposition at the limbus have also been noted in some cats. Weakness, lethargy, and failure to grow have been noted, and affected animals have a higher incidence of being stillborn.

With inherited hyperchylomicronemia, there are marked elevations in serum triglyceride and cholesterol, and blood will often have a "cream tomato soup" appearance (Figure 10). In one study, the mean cholesterol concentration in 24 cats with inherited hyperchylomicronemia was 6.6 mmol/L (reference range 1.1 - 5.0 mmol/L)(255 mg/dL; range 42 - 193 mg/dL), and the mean triglyceride concentration was 10.02 mmol/L (reference range 0.2 - 0.6 mmol/L) (888 mg/dL; reference range 18 - 53 mg/dL).

Figure 10. Blood appearance in case of hyperchylomicronemia. With inherited hyperchylomicronemia, there are marked elevations in serum triglyceride and cholesterol, and blood will often have a "creamy tomato soup" appearance.

Serum concentration of triglyceride can be extremely elevated in some cats, with triglyceride concentrations reported near 147 mmol/L (13,000 mg/dL) (Bauer & Verlander, 1984). The condition is characterized by a great excess of chylomicrons (Bauer & Verlander, 1984), or by excess chylomicrons with slight increase in VLDL (Jones et al., 1986). This condition most closely resembles Type I hyperlipidemia in humans. Atherosclerosis has not been noted in cats with inherited hyperchylomicronemia despite the lipoprotein abnormalities (Johnstone et al., 1990).

Lipoprotein lipase activity is virtually absent in the inherited hyperchylomicronemia caused by a Gly412Arg missense mutation of the LPL gene of cats. The decrease in LPL activity is not due to a lack of apoprotein C-II which is necessary for LPL activation (Watson et al., 1992). Peritz et al. (1990) report that the LPL mass is normal in affected cats, but speculate the LPL protein is abnormal and cannot bind to endothelium. However, Ginzinger et al. (1996) reported an absence of circulating mass of LPL but did find mutant mRNA forms in tissues. A similar defect of LPL has been noted in mink with severe hyperchylomicronemia, normal LPL mass, but no LPL activity (Christophersen et al., 1997).

The cause of hyperchylomicronemia has been shown to be a mutation in the LPL gene (Ginzinger et al., 1996), and both homozygotes and heterozygotes for LPL deficiency have been described (Ginzinger et al., 1999). Homozygotes tend to be more severely affected than heterozygotes, and the severity of hyperchylomicronemia and hypertriglyceridemia is dependent on the magnitude of decrease in LPL activity. In a brother to a severely affected kitten, hypertriglyceridemia was observed but not of the same magnitude as in the severely affected kitten, and LPL activity was decreased but not to the same degree (Bauer & Verlander, 1984).

Adult cats that are homozygous for LPL deficiency have a significantly decreased body fat mass as compared to those that are clinically normal or heterozygotes for LPL deficiency (Backus et al., 2001). Homozygotes born to homozygote dams had a significantly lower body fat mass than homozygotes born to heterozygote dams. Thus the body fat mass depends not only on the lipoprotein status of the cat, but also on the LPL status of the dam.

Another condition that has characteristics similar to inherited hyperchylomicronemia has been observed (Gunn-Moore et al., 1997). Transient hyperlipidemia and anemia has been noted in litters of kittens with marked increase in chylomicrons and moderate increase in VLDL. After resolution of hyperlipidemia with the feeding of diets containing 9% fat as-fed (approximately 28 g fat/ 1000 kcal), LPL activity was only mildly lower in affected kittens as compared to normal kittens. These kittens did not exhibit the LPL gene mutation that has been shown in the inherited hyperchylomicronemia that has been well characterized. This suggests the presence of a separate distinct primary hyperlipidemia.