Current Status of Familial LCAT Deficiency in Japan

Abstract

around the same time, a patient with deficiency of this enzyme was identified in Norway. A 33-year-old woman in a hospital in Oslo was suspected of having chronic nephritis due to proteinuria and exhibited corneal opacity, anemia, and slight hypoalbuminemia, though renal function was normal. Renal biopsy revealed presence of foam cells in the glomerular tufts. Plasma total cholesterol and triglyceride levels were high but most of the cholesterol was found not to be esterified and further biochemical analyses Copyright©2021 Japan Atherosclerosis Society This article is distributed under the terms of the latest version of CC BY-NC-SA defined by the Creative Commons Attribution License.

Two Cases of Acquired High-Density Lipoprotein Deficiency with Immunoglobulin G4-Related Lecithin–Cholesterol Acyltransferase Autoantibody

“…The specimen for light microscopy contained six glomeruli, one of which was sclerosed. Similar to the congenital LCAT deficiency with proteinuria 2,13) , almost all of the glomeruli had mesangial proliferation and lipid deposition and accumulation of foam cells. Furthermore, spike formation, bubbling, and double contouring in the glomerular basement membrane (GBM) were observed (Fig.…”

“…Thus, a loss or reduction in LCAT function results in abnormal HDL conditions, including low to deficient levels. The three major characteristics of familial LCAT deficiency (FLD) are corneal opacity, anemia, and kidney disease, but there are various conditions of clinical phenotypes by primary gene mutations 1,2) . Fish-eye disease, which is also a primary LCAT gene mutation disease, is characterized by HDL deficiency with severe corneal opacity but without other features.…”

LCAT-trial-24 weeks: Protocol for a clinical study to evaluate the safety of regenerative medicine and gene therapy by the autologous transplantation of human lecithin:cholesterol acyltransferase gene-transduced human pre-adipocytes

“…This trial was planned to evaluate safety of the investigational product, LCAT gene-transduced autologous pre-adipocytes essentially. About 20 mutations have been identified for familial LCAT deficiency thus far in Japan [ 14 ], according to published literature; however, the number of patients who were introduced to Chiba University Hospital from other institutions as possible candidates is extremely limited. Thus, the target number of cases (number of administered cases) was set to three, with regulatory strategy consultation of the PMDA, based on the feasibility of enrollment in Japan.…”

“…Since the investigational product are intended to supply therapeutic wild-type LCAT protein, patients may generate antibodies against the LCAT protein as well as other ERTs. Patients who are not expected to express full-length LCAT protein due to frameshift or the appearance of a stop codon by nonsense or insertion/deletion mutations in the LCAT gene will be excluded from this clinical trial in order to minimize the risk of generation of antibodies against LCAT protein, since only two such mutations have been found among the approximately 20 mutations that have so far been previously identified in Japan [ 14 ].…”

Transitional Medicine of Intractable Primary Dyslipidemias in Japan

“…In Specific Pediatric Chronic Diseases, it is registered as "HDL deficiency," but there were 0 patients in 2019 5) . LCAT deficiency is divided into two phenotypes: familial LCAT deficiency (FLD) and fish eye disease (FED) [42][43][44] . The frequency of FED is reported to be approximately one-third that of FLD 42,44) .…”