Neurodegeneration in familial chylomicronemia syndrome

Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive disorder associated with markedly elevated triglyceride concentration and acute pancreatitis, but neuropathic pain and cognitive dysfunction are also increasingly recognized. This study undertook detailed quantification of somatic and autonomic neuropathy in participants with FCS.

Sixteen individuals with FCS and 16 age and sex-matched controls underwent assessment of the lipid profile, neuropathic symptoms and disability, vibration perception, corneal confocal microscopy (CCM), and cardiac autonomic reflex testing.

Age (36.4 [26.5-47.2] vs 36.7 [31.3-46.9] years, P = .7), gender distribution (males 44% [n = 7] vs 50% [n = 8], P = .7), body mass index (23.7 [20.3-27.1] vs 24.7 [22.3-27.2] kg/m², P = .5), and glycosylated hemoglobin (36.0 [32.5-39.2] vs 36.8 [33.0-38.0] mmol/mol, P = .9) were comparable between participants with FCS and controls. Triglycerides were significantly higher (23.7 [17.4-34.8] vs 1.0 [0.7-1.3] mmol/L, P < .001), whilst low-density lipoprotein cholesterol (0.9 [0.7-1.2] vs 2.7 [2.3-3.1] mmol/L, P < .001) and high-density lipoprotein cholesterol (0.4 [0.3-0.6] vs 1.5 [1.3-1.9] mmol/L, P < .001) were lower in participants with FCS. The Neuropathy Symptom Profile Score (4 [0-14] vs 0, P = .003), Neuropathy Disability Score (1 [0-3.5] vs 0, P = .01), and vibration perception threshold (6.5 [4.7-8.1] vs 3.0 [2.0-3.5] volts, P < .001) were higher, whilst corneal nerve fiber density (30.2 [27.3-32.3] vs 37.0 [32.5-38.5] no./mm², P < .001), corneal nerve branch density (54.1 [42.0-76.6] vs 100.5 [67.0-147.1] no./mm², P < .001), corneal nerve fiber length (20.0 [18.3-25.5] vs 27.5 [23.9-34.3] mm/mm², P < .001), deep breathing heart rate variability (17.0 [14.2-28.0] vs 29.5 [25.2-34.7] beats/min, P = .002), and expiration to inspiration ratio (1.18 [1.14-1.29] vs 1.36 [1.25-1.41], P = .001) were lower in participants with FCS compared to controls.

FCS is associated with neuropathic symptoms, elevated vibration perception, small nerve fiber damage, and cardiac autonomic dysfunction.