Lecithin-cholesterol acyltransferase deficiency E78.6; N08.4

Autosomal recessive lecithin-cholesterol-acyltransferase (LCAT) deficiency is a congenital disorder of fat metabolism caused by mutations in the LCAT gene (16q22.1). So far, > 85 mutations have been identified in the LCAT gene (16q22.1).

The hereditary LCAT (lecithin-cholesterol-acyltransferase) deficiency leads to 2 phenotypically different diseases:

• Familial LCAT deficiency: corneal opacities, anaemia and renal insufficiency(nephrotic syndrome), reduced concentration of HDL cholesterol.
• Fish eye disease (LCAT deficiency is a partial deficiency): corneal opacities and arteriosclerosis, reduced concentration of HDL cholesterol (Ustaoglu M et al. 2019).

Both known phenotypes in familial LCAT deficiency are very rare: 70 reported cases of familial LCAT deficiency; 30 cases of fisheye disease; most of the diseases have been described in Europe, Japan and Canada.

Mutations in the LCAT gene (16q22.1) can lead to LCAT deficiency and lack of activity of the LCAT enzyme. Cholesterol acetyltransferase catalyzes the formation of cholesterol esters in lipoproteins. LCAT deficiency leads to an increase in the concentration of cholesterol and triacylglycerols in plasma and to hypoalphalipoproteinemia (Tobar HE et al. 2019). The plasma is visibly cloudy or milky. There is accumulation of non-esterified cholesterol and deposits e.g. in cornea, erythrocytes and kidney.

Note: 70% of the cholesterol transported in lipoproteins in human blood is present as cholesterol ester. In this form it can be easily broken down in the liver. LCAT is therefore indispensable in fat metabolism.

Most patients are diagnosed in adulthood.

The clinical picture is characterized by the symptom triad: anemia, glomerulopathy (nephrotic syndrome) and corneal opacities.

In the eyes there is diffuse nebulous opacity (circumscribed lipid deposition) of the corneal stroma on both sides. These are composed of tiny, punctiform individual clouding points and show a ring-shaped compression in the corneal periphery with blurred boundaries.

The corneal opacity is the only obligatory clinical symptom, especially in the case of an incomplete LCAT deficiency, which is also uniform and pathognomonic in nature. This type of corneal opacity is a real leading symptom of LCAT deficiency.

Less common symptoms are atherosclerosis, hepatomegaly, splenomegaly and lymphadenopathies.

Clinic, laboratory; the definitive diagnosis requires DNA diagnostics in the LCAT gene and functional analysis of the gene product.

Prenatal diagnostics: prenatal diagnostics is possible. The families concerned should be offered genetic counselling.

Nutritional therapeutic approaches consist in a reduction of the cholesterol intake.

In the case of fisheye disease, corneal transplantation or "penetrating keratoplasty" can be considered.

Possible kidney failure with complete LCAT deficiency.

Partial LCAT deficiency (fisheye disease) is a visual impairment due to corneal clouding.

Occasionally, an acquired LCAT deficiency was also described. The cause is autoantibodies against LCAT. These patients are conspicuous by a nephrotic syndrome due to a membranous glomerulopathy (Ishibashi R et al. 2018).

1. Delteil C et al (2019) Glomerulopathy associated with lecithin-cholesterol-acyltransferase deficiency: A case report and literature review. Ann Pathol 39:172-176.
2. Ishibashi R et al (2018) Immune-mediated acquired lecithin-cholesterol acyltransferase deficiency: A case report and literature review. J Clin Lipidol 12:888-897.
3. Tobar HE et al (2019) Identification and functional analysis of missense mutations in the lecithin cholesterol acyltransferase gene in a Chilean patient with hypoalphalipoproteinemia. Lipids Health 18:132.
4. Ustaoglu M et al (2019) Ocular and Genetic Characteristics Observed in Two Cases of Fish-Eye Disease. Cornea 38:379-383.
5. Viestenz E et al (2003) Ocular manifestation of LCAT deficiency - a clinical-histopathological correlation. Klin Monatsbl Ophthalmology 220: 499-502
6. Zemsky CJ et al (2019) Case Report: Management of Corneal Clouding from Lecithin: Cholesterol Acyltransferase Deficiency. Optom Vis Sci 96:137-141.