LCAT deficiency
The human LCAT gene is present on
chromosome 16 (region 16q 22)
(1). Mutations in the LCAT gene reportedly cause two rare
inherited
metabolic disorders, classical Familial LCAT Deficiency (FLD, OMIM#
245900) and
Fish-Eye Disease (FED, OMIM# 136120). The differential diagnosis of FLD
and FED
is made by highly specialized laboratories*, and is
based on stringent biochemical criteria
(in homozygous or compound heterozygous carriers) and in vitro
expression of
the mutant enzyme (in heterozygous carriers) (2,3). Both FLD and FED
cases have
a marked reduction of plasma HDL levels, but do not seem to be at high
cardiovascular risk (3). More than 70 different mutations in the human LCAT
gene have been identified to now (see mutation
database).
FLD was first described by Norum and Gjone in 1967 (4). In FLD cases,
LCAT is not synthesized or is completely inactive, and unesterified
cholesterol accounts for most of plasma cholesterol. Clinically, the
lipid accumulation in different tissues leads to progressive
corneal opacity, anemia and focal glomerulosclerosis, which can
progress to complete renal failue starting from the the third-fourth
decade of life, requiring hemodialysis and eventually kidney
transplantation (5). FED was first described by Carlson and Philipson
in 1979 (6). In FED cases, LCAT does not esterify choolesterol in HDL,
but esterifies cholesterol in other lipoproteins; subnormal levels of
esterified cholesterol are present in plasma. The clinical
phenotype is usually milder than in FLCD cases (5).
*Center E. Grossi Paoletti, Milano, Italy. For informations