Neurodegeneration in familial chylomicronemia syndrome

Background & Objectives Familial chylomicronaemia 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 recognised. This study undertook detailed quantification of somatic and autonomic neuropathy in participants with FCS. Methods Sixteen individuals with FCS and sixteen 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. Results Age [36.4 (26.5 – 47.2) vs. 36.7 (31.3 – 46.9) years, p = 0.7], gender distribution [males 44% (n=7) vs. 50% (n=8), p = 0.7], body mass index (BMI) (23.7 [20.3-27.1] vs. 24.7 [22.3-27.2] kg/m 2 , p = 0.5), and HbA1c (36.0 [32.5 – 39.2] vs. 36.8 [33.0 – 38.0] mmol/mol, p = 0.9) 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 <0.001), whilst LDL-C [0.9 (0.7 – 1.2) vs. 2.7 (2.3 – 3.1) mmol/L, p <0.001) and HDL-C [0.4 (0.3 – 0.6) vs 1.5 [1.3 – 1.9] mmol/L, p <0.001) were lower in participants with FCS. The Neuropathy Symptom Profile score [4 (0 – 14) vs 0, p =0.003], Neuropathy Disability Score [1 (0 – 3.5) vs 0, p = 0.01] and vibration perception threshold [6.5 (4.7 – 8.1) vs 3.0 (2.0 – 3.5) volts, p <0.001] were higher, whilst corneal nerve fibre density [30.2 (27.3 – 32.3) vs 37.0 (32.5 – 38.5) no./mm 2 , p <0.001], corneal nerve branch density [54.1 (42.0 – 76.6) vs 100.5 (67.0 – 147.1) no./mm 2 , p <0.001], corneal nerve fibre length [20.0 (18.3 – 25.5) vs 27.5 (23.9 – 34.3) mm/mm 2 , p <0.001], deep breathing heart rate variability [17.0 (14.2 – 28.0) vs 29.5 (25.2 – 34.7) beats/min, p =0.002] and E–I ratio [1.18 (1.14 – 1.29) vs 1.36 (1.25 – 1.41), p =0.001] were lower in participants with FCS compared to controls. Conclusion FCS is associated with neuropathic symptoms, elevated vibration perception, small nerve fibre damage and cardiac autonomic dysfunction.