2026-02-21 | Lecithin-cholesterol acyltransferase deficiency with the finding of "zebra bodies": A diagnostic challenge in the context of suspected Fabry disease.
Lecithin-cholesterol acyltransferase (LCAT) deficiency is a rare autosomal recessive disorder resulting from mutations in the LCAT gene, which leads to abnormal lipoprotein metabolism. This results in markedly reduced high-density lipoprotein cholesterol and the accumulation of lipoprotein X, leading to renal, corneal, and hemolytic damage. Two clinical variants have been described: familial LCAT deficiency (FLD) and fish-eye disease (FED). We report the case of a 41-year-old male with a history of hypertension, tinnitus, and progressive hearing loss, who presented with bilateral corneal opacity since childhood. Laboratory studies revealed significant proteinuria (2.56 g/24 h), preserved renal function (creatinine 0.85 mg/dL), mild anemia (Hb 10.2 g/dL), and extremely low HDL cholesterol (1.3 mg/dL). Renal biopsy showed focal segmental glomerulosclerosis and mesangial expansion. Electron microscopy demonstrated concentric lamellar inclusions known as "zebra bodies," a finding typically associated with Fabry disease. However, α-galactosidase A activity was normal, and genetic testing for Fabry disease was negative. Further genetic analysis identified the variant c.757 p.(Gln253Argfs*11) in the LCAT gene, confirming the diagnosis of familial LCAT deficiency. This case highlights the importance of differentiating LCAT deficiency from Fabry disease, given their overlapping clinical and histological features. Moreover, it represents the first description of "zebra bodies" in LCAT deficiency, emphasizing the diagnostic complexity and the need for a multidisciplinary approach to ensure accurate diagnosis and appropriate management.
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2026-01-19 | Lecithin-Cholesterol Acyltransferase Deficiency as a Rare Cause of Bilateral Corneal Opacities: A Case Report of a Novel Frameshift Mutation.
Lecithin-cholesterol acyltransferase (LCAT) deficiency is a rare autosomal recessive disorder of lipid metabolism characterized by corneal opacification, hemolytic anemia, and chronic kidney disease. We describe the ophthalmic, systemic, and genetic findings of a patient with LCAT deficiency and report a novel frameshift mutation in the LCAT gene. Ophthalmic findings may represent the first clinical sign and guide the diagnosis. A 50-year-old white male with end-stage renal disease on hemodialysis and a history of recurrent hemolytic anemia was referred for bilateral corneal opacities. Despite diffuse opacification involving all corneal layers, his best corrected visual acuity remained 20/20 in both eyes with normal color vision, although contrast sensitivity was reduced. Laboratory testing revealed normocytic, normochromic anemia, low HDL cholesterol, and reduced apolipoprotein A levels. Genetic analysis identified compound heterozygosity in the LCAT gene: a novel frameshift variant c.580_598del p.(Ala194Serfs*64), classified as likely pathogenic, and the previously described missense variant c.619G>A p.(Gly207Ser), also classified as likely pathogenic. This case highlights the importance of considering metabolic disorders in the differential diagnosis of bilateral corneal opacities and expands the genetic spectrum of LCAT deficiency by reporting a novel frameshift mutation.
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2026-01-16 | Quantitative Assessment of Visual Function in Japanese Patients With Lecithin-Cholesterol Acyltransferase Gene Abnormalities: A Case-Control Study.
Introduction Fish-eye disease (FED) and familial lecithin-cholesterol acyltransferase (LCAT) deficiency (FLD) are rare. The aim of this study was to compare visual function between patients with LCAT abnormalities - namely, FED and FLD - and healthy controls. Methods This retrospective, comparative case-control study included four patients with FLD or FED (LCAT group) who presented with cloudy corneas at Miyata Eye Hospital between 2018 and 2024. Four age- and sex-matched individuals with normal results on ophthalmic examination were included as controls. We reviewed medical records for best-corrected visual acuity (BCVA), corneal astigmatism, forward light scattering, and contrast sensitivity. The parameters were compared between the groups. Results Sixteen eyes of eight women were included, including eight eyes of four patients with cloudy corneas in the LCAT group (two with FLD and six with FED) and eight eyes of four controls. The mean BCVA and corneal astigmatism revealed no significant intergroup differences. However, forward scattering was significantly higher in the LCAT group than in the control group (p = 0.007). The area under the log-contrast sensitivity function was significantly lower in the LCAT group than in the control group (p = 0.017). Conclusions Despite normal BCVA, patients with LCAT abnormalities (FLD and FED) showed considerably increased forward light scattering and decreased contrast sensitivity compared with the controls, indicating subtle but substantial visual functional impairment.
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