LCAT promotes transfer of excess cholesterol from peripheral tissues to the liver, and a deficiency of this enzyme results in accumulation of unesterified cholesterol in the plasma and tissues. This, in turn, leads to atherosclerosis, renal insufficiency, early corneal arcus, and nebular corneal clouding composed of minute focal lipid deposits.
LCAT deficiency and fish eye disease are allelic variants of the same genetic locus on band 16q22.1. In fish eye disease, LCAT levels are normal, but the enzyme does not function properly. Tangier disease is characterized by a complete absence of serum high-density α-lipoproteins. The gene responsible for this disease maps to 9q22–q31.
LCAT deficiency, fish eye disease, and Tangier disease are rare autosomal recessive conditions. Familial LCAT deficiency is characterized by peripheral arcus and nebular stromal haze made up of myriad minute focal deposits of lipid that appear early in childhood but do not interfere with vision (Fig 8-3). Fish eye disease features obvious corneal clouding from minute gray-white-yellow dots that progress from the periphery to the central cornea to decrease vision. Tangier disease features very large orange tonsils; enlarged liver, spleen, and lymph nodes; hypocholesterolemia; and abnormal chylomicron remnants. Affected corneas show diffuse clouding and posterior focal stromal opacities but no arcus. Neuropathy leads to lagophthalmos and corneal sequelae.
Figure 8-3 Clinical photograph from a patient with familial lecithin-cholesterol acyltransferase (LCAT) deficiency, showing peripheral arcus and nebular stromal haze.
(Courtesy of Gerald Zaidman, MD.)
LABORATORY EVALUATION AND MANAGEMENT
The serum lipid profile shows characteristic low levels of HDL (markedly low in Tangier disease). Recognition of hypolipoproteinemia can allow the clinician to make appropriate referrals and encourage the patient to seek genetic counseling.
Excerpted from BCSC 2020-2021 series: Section 10 - Glaucoma. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.