Fish-eye disease

Famiiiai aipha-iipoprotein deficiency Tangier disease Fish-eye disease Apo-A-i deficiencies All have low or near absence of HDL. Tendency toward hypertriacylglycerolemia as a result of absence of apo C-ll, causing inactive LPL. Low LDL levels. Atherosclerosis in the elderly. 

LCAT catalyzes the transfer of a preferentially unesterified fatty acid from the sn-2 position of phosphatidylcholine to the 3/i-hydroxy group of cholesterol, and thereby produces lysophosphatidylcholine and a cholesteryl ester [50]. Depending on the mutation in the LCAT gene, homozygous or compound heterozygous patients present with one of two clinical phenotypes, classical LCAT deficiency or fish-eye disease [58, 85]. Classical LCAT deficiency is caused by a broad spectrum of missense and non-sense mutations that interfere with the synthesis or secretion or affect the catalytic activity of LCAT [10]. Fish-eye disease is caused by a limited number of missense point mutations that alter the surface polarity, and thereby interfere with the binding of the enzyme to apoA-I containing lipoproteins [77]). 

Biochemically, both patients with classical LCAT deficiency and fish-eye disease present with very low levels of HDL cholesterol (< 0.3 mmol/1), although some pa-... 

LCAT acts preferentially on lipids transported by HDL (so-called a-LCAT activity), but also on lipids transported by apoB-containing lipoproteins (so-called jS-LCAT activity) [58, 85]. In practice, LCAT activity is measured either as the activity required to esterify radioactive cholesterol that has been exogenously incorporated into native HDL or into artificial HDL-like particles (a-LCAT activity) or which has been equilibrated with endogenous lipoproteins of the plasma sample (cholesterol esterification rate, CER) [21, 58, 85]. Several variations of these assays have been reported, some of which are available as commercial test kits (e.g., Roar Biomedical, New York, USA). In addition, LCAT concentration can be determined by either laboratory-made tests or by a commercial ELISA kits [57]. However, the decrease in LCAT concentration is difficult to judge since it also decreases secondary to HDL deficiency due to causes other than LCAT deficiency. Plasma from patients with LCAT deficiency fails to esterify radioactive cholesterol provided by any substrate. By contrast, plasmas of patients with fish-eye disease show a near-normal cholesterol ester-fication rate but have a selective inability to esterify radioactive cholesterol provided to plasma with native HDL or reconstituted HDL (a-LCAT activity) [58, 85]. 

Patients with classical LCAT deficiency fail to esterify cholesterol in any substrate and hence have both an undetectable or very low cholesterol esterification rate and a-LCAT activity. Patients with fish-eye disease usually have a normal cholesterol esterification rate and a selective a-LCAT deficiency. 

Patients with classical LCAT deficiency show an increased proportion of unesterified cholesterol in plasma (80-100%). By contrast, the plasma from patients with fish-eye disease has a slightly elevated proportion of unesterified cholesterol (up to 70%). 

Funke H, Eckardstein A von, Pritchard PH, Albers JJ, Kastelein JJ, Droste C, Assmann G (1991) A molecular defect causing fish eye disease an amino acid exchange in lecithin-cholesterol acyltransferase (LCAT) leads to the selective loss of alpha-LCAT activity. Proc Natl Acad Sci U S A 88 4855-4859... 

Santamarina-Fojo S, Hoeg J, Assmann G, Brewer HJ (2000) Lecithin cholesterol acyltrans-ferase deficiency and fish-eye disease. In Scirver C, Beaudet A, Sly E, Valle D (eds) The Metabolic and Molecular Bases of Inherited Disease, 8th edn. McGraw-Hill, New York, pp 2817-2833... 

C4. Carlson, L. A., and Philipson, B., Fish-eye disease. A new familial condition with massive corneal opacities and dyslipoproteinemia. Lancet 1, 921-924 (1979). 

F18. Forte, T. M., and Carlson, L. A., Electron microscopic structure of serum lipoproteins from patients with fish eye disease. Arteriosclerosis 4, 130—137 (1984). 

Familial alpha-lipoprotein deficiency (Tangier disease, fish-eye disease, apo-A-I and C-III deficiencies)... 

Rare forms of lipoprotein disorders may include hypobeta-lipoproteinemia, abetalipoproteinemia, Tangier disease, LCAT deficiency (fish-eye disease), cerebrotendinous xanthomatosis (CTX),... 

Familial lecithin Cholesterol acyltransferase deficiency, including fish eye disease, K. R. Norum, E. Gjone and J. 

HDL deficiency may, in many cases, be a secondary syndrome, i.e. linked to hypertriglyceridemia, nicotine abuse, physical inactivity, etc. The primary deficiencies are also numerous Tangier disease, fish-eye disease, A-I-C-III deficiencies (variants I and II), some of the mutants, and HDL processing defects. 

Fish-eye disease (FED) was detected in a Swedish kindred. Severe corneal opacification and a marked reduction of HDL and Apo A-I are its major features [5]. Studies on the genome have failed to detect any significant alterations [27]. FED, similarly to the A-I-Milano mutant, is characterized by the presence of very small HDL particles. By gradient gel electrophoresis, subjects with FED show HDL of 3b-3 c mobility, vs... 

Carlson LA, Holmquist L (1985) Evidence for deficiency of high-density lipoprotein lecithin-cholesterol acyltransferase activity (a-LCAT) in Fish Eye disease. Acta Med Scand 218 189-196... 

Rees A, Stocks J, Shoulders C, Carlson LA, Baralle FE, Galton DJ (1984) Restriction enzyme analysis of the apolipoprotein A-I gene in Fish Eye Disease and Tangier Disease. Acta Med Scand 215 235-237... 

Table 28.8.2. Partial LCAT deficiency (Fish-eye disease) ...

Hypo-alphalipoproteinemia Tangier disease Fish eye disease Ci,TAGi HDLi LCAT deficiency Apo A-l i, apo C-lll i Abnormal apo A-l, and apo A-ll metabolism... 

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