Choroideremia is a Systemic Disease with Retinal Crystals, Lymphocyte Crystals and Serum Lipid Abnormalities

Abstract

Purpose: Choroideremia (CHM) is a well known X-linked recessive retinal dystrophy characterized by a progressive degeneration of the choriocapillaris, retinal pigment epithelium (RPE) and photoreceptors caused by mutations in REP1 (Rab Escort Protein 1). We describe five families with Choroideremia, who have crystals in the retina and in their lymphocytes and abnormalities in their lipid profile. The aim of our study is to show that Choroideremia is a systemic disease.

Methods: Five male patients of French Canadian background were recruited. They ranged in age from 26 to 60 years old. Characterization of the phenotypes was done through history, physical exam, Goldmann visual field testing and fundus photography. Heidelberg Spectralis OCT and fundus autofluorecence were used to look for retinal crystals and abnormalities in lipofuscin metabolism. Peripheral blood samples were drawn. We first determined fasting lipid profiles and plasma total lipid fatty acid profiles. We then fixed the blood with 2.5% glutaraldehyde in 0.1M sodium cacodylate buffer for electron microscopy (EM) analysis. Sanger sequencing was done to identify the REP1 mutation.

Results: Clinically, the CHM patients have varying degree of fundus changes. Severity of the condition correlated with the patient’s age. On the OCT, all our CHM study patients had retinal crystals in variable size and number. The fasting lipid profiles showed an elevation in triglycerides and total cholesterol. Total lipid fatty acid profile shows elevations in unsaturated fatty acids, two standard deviations above normal range: C14:2 (n-6, n-9), C18:1(n-9) and C25:1(n-9). All patients showed a decrease in total trans fatty acids. EM analysis showed lymphocyte crystals. Sanger sequencing confirmed that all patients had REP1 mutations and thus Choroideremia.

Conclusions: This study showed for the first time that Choroideremia is a systemic disease with significant lipid abnormalities. It further demonstrates that patients with Choroideremia have crystals in both the retina and in peripheral lymphocytes. The elevations seen in total lipid fatty acid profile suggest an up regulation of the Δ-9 desaturase enzyme. We postulate that the crystals seen in the retina and lymphocytes are due to fatty acid deposition. The next step will be to determine the content of lymphocyte crystals and to counsel the CHM patients about their systemic disease.

Keywords: 452 choroid • 696 retinal degenerations: hereditary • 695 retinal degenerations: cell biology