Lecithin cholesterol acyltransferase deficiency is a disorder of lipoprotein metabolism. The disease has two forms: Familial LCAT deficiency, in which there is complete LCAT deficiency, and Fish-eye disease, in which there is a partial deficiency.Lecithin cholesterol acyltransferase catalyzes the formation of cholesterol esters in lipoproteins. Signs and symptoms
Symptoms of the familial form include visual impairment caused by diffuse corneal opacities, target cell hemolytic anemia, and kidney failure. Less common symptoms include atherosclerosis, hepatomegaly (enlarged liver), splenomegaly (enlarged spleen), and enlarged lymph nodes.Fish-eye disease is less severe and most commonly presents with impaired vision due to corneal opacification. It rarely presents with other findings, although, atherosclerosis, hepatomegaly, splenomegaly, and lymphadenopathy can occur. Carlson and Philipson found that the disease was named so because the cornea of the eye was so opaque or cloudy with dots of cholesterol that it resembled a boiled fish.If an individual only carries one copy of the mutated gene, they typically do not show symptoms. Pathophysiology
A deficiency of LCAT causes accumulation of unesterified cholesterol in certain body tissues. Cholesterol effluxes from cells as free cholesterol and is transported in HDL as esterified cholesterol. LCAT is the enzyme that esterifies the free cholesterol on HDL to cholesterol ester and allows the maturation of HDL. LCAT deficiency does not allow for HDL maturation resulting in its rapid catabolism of circulating apolipoprotein A1 and apolipoprotein A2. The remaining form of HDL resembles nascent HDL.The LCAT glycoprotein produces lysophosphatidylcholine and cholesterol ester and binds to lipoproteins after being secreted by the liver.
They are still used only rarely, although newer and better-tolerated agents of this class have been developed. The safety profile is different with reversible monoamine oxidase inhibitors, such as moclobemide, where the risk of serious dietary interactions is negligible and dietary restrictions are less strict.It is unclear whether antidepressants affect a persons risk of suicide. For children, adolescents, and probably young adults between 18 and 24 years old, there is a higher risk of both suicidal ideations and suicidal behavior in those treated with SSRIs. For adults, it is unclear whether SSRIs affect the risk of suicidality. One review found no connection; another an increased risk; and a third no risk in those 25–65 years old and a decreased risk in those more than 65. A black box warning was introduced in the United States in 2007 on SSRIs and other antidepressant medications due to the increased risk of suicide in people younger than 24 years old. Similar precautionary notice revisions were implemented by the Japanese Ministry of Health. Other medications and supplements
The combined use of antidepressants plus benzodiazepines demonstrates improved effectiveness when compared to antidepressants alone, but these effects may not endure. The addition of a benzodiazepine is balanced against possible harms and other alternative treatment strategies when antidepressant mono-therapy is considered inadequate.Ketamine may have a rapid antidepressant effect lasting less than two weeks; there is limited evidence of any effect after that, common acute side effects, and longer-term studies of safety and adverse effects are needed.