CArotenoid in hypoChOlesterolemia

Summary

Hypobetalipoproteinemias (HBL) represent a heterogeneous group of disorders characterized by reduced plasma levels of plasmatic lipids (mainly triglycerides, total cholesterol (TC), LDL-cholesterol (LDL-C), and apolipoprotein B (apoB)) below the 5th percentile of the general population adjusted for age, gender. HBL may be attributed to inherited disorders caused by mutations in several known genes. Intestinal recessive HBL includes abetalipoproteinemia (ABL) (OMIM 200100) and Chylomicron Retention Disease (CMRD) (OMIM 246700) - also called Anderson's disease. Those two recessives form of HBL are the ones considered in this study. ABL is due to mutations in the Microsomal Triglyceride Transfer Protein (MTTP) gene which is required for the assembly and secretion of apoB-containing lipoproteins: Low-Density Lipoprotein (LDL) and chylomicrons (CM) in both liver and intestine. Similarly, CMRD is due to mutations in the Sar1b gene encoding the Sar1b protein involved in the control of the intracellular trafficking of CMs in COPII-coated vesicles. Due to a defect in Apolipoprotein B-containing lipoproteins these diseases are characterized by dietary lipids and fat-soluble vitamins (A, D, E, K) malabsorption inducing digestive and growth disorders from birth. In parallel, neurological manifestations may appear, mainly as a consequence of vitamin E and A deficiencies.

Ophthalmological disorders are inconstant, with many patients being asymptomatic until adulthood. Loss of night or color vision are the first symptoms associated with retinal degeneration. Without treatment with high doses of vitamins, retinal degeneration can lead to blindness. The exact biological mechanism still remains unknown. Indeed, cases described in the scientific literature demonstrate that early treatment with high doses of vitamin E and A can stop or prevent neurological complications in the vast majority of patients; however, ophthalmic complications have a more versatile response.

Thus, despite early vitamin supplementation, several cases of adolescent or adult patients with vision impairment in the form of retinitis pigmentosa have been reported. This so-called secondary retinitis pigmentosa is characterized by a progressive loss of photoreceptors and a dysfunction of the pigmentary epithelium resulting in a progressive and gradual loss of vision, usually leading to blindness. Interestingly, primary (i.e., genetic) retinitis pigmentosa are characterized by "macula lutea" atrophy composed of two lipophilic molecules from the carotenoid xanthophyll family lutein and zeaxanthin, also known as macular pigments. Moreover, preliminary data seem to show that the patients considered for this study, present decreased plasmatic carotene concentrations as well as plasmatic vitamin E concentrations largely lower than the threshold of normality.

Thus, even if early treatment seems to prevent major ophthalmic complications, it does not provide total ophthalmic protection, which suggests the involvement of other factors among which carotenoids could occupy a prominent place given their essential role in maintaining the integrity of the macula.

Conditions

• Primary Intestinal Hypocholesterolemia
• Abetalipoproteinemia
• Chylomicron Retention Disease

Interventions

BIOLOGICAL

Characterization of carotenoid status and plasma levels of oxidative stress markers in patients (case group only)

Carotenoid status will be determined by measuring plasma and erythrocyte concentrations of lutein and zeaxanthin obtained during an annual blood draw. These molecules will be analyzed by high performance liquid chromatography. The oxidative stress markers will be measured, in the blood sample already collected, thanks to specific assay kits: Erythrocyte reduced glutathione, Superoxide dismutase (SOD), Glutathione peroxidase (GPx), Plasma and erythrocyte malondialdehyde, Plasma vitamin C, Plasma oxidized cholesterol, F2-isoprostanes. This study does not result in any change in patient management, but requires the collection of an additional volume of blood (14 ml of study-specific blood) during the annual blood draw performed as part of routine patient follow-up.

OTHER

Characterization, evaluation and comparison of macular pigment density

The macular pigment optical density (OD) will be determined by an additional photograph during the fundus usually performed for annual follow-up through two-wavelength autofluorescence imaging. Indeed, the measurement of the optical density consists of an additional post-examination analysis of additional retinal images obtained during the fundus performed for the patients' ophthalmologic follow-up.

Sponsors & Collaborators

• Hospices Civils de Lyon

  lead OTHER

Principal Investigators

• Peretti Noël, Pr · Hospices Civils de Lyon

Eligibility

Min Age

6 Years

Max Age

50 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2022-06-30

Primary Completion

2024-11-07

Completion

2024-11-07

Countries

• France

Study Locations