|Year : 2021 | Volume
| Issue : 2 | Page : 178-180
Bilateral corneal clouding of lecithin cholesterol acyltransferase deficiency – A rare case report
S Uma Maheshwari1, M Muthayya1, P Thiyagarajan2, G Barathi1
1 Department of Ophthalmology, Sri Ramachandra Institute of Higher Education and Research, Chennai, Tamil Nadu, India
2 Department of Ophthalmology, Velammal Medical College Hospital and Research Institute, Madurai, Tamil Nadu, India
|Date of Submission||10-Dec-2020|
|Date of Acceptance||20-Jan-2021|
|Date of Web Publication||24-Jun-2021|
Dr. S Uma Maheshwari
No. 13/6, Mudichur Road, Old Perungalathur, Chennai - 600 063, Tamil Nadu
Source of Support: None, Conflict of Interest: None
A 44-year-old female patient presented to our department with bilateral corneal opacity since childhood. History of similar complaints was elicited among her family members. Best-corrected visual acuity in both eyes was 6/9 with bilateral stromal corneal clouding extending from limbus to limbus, with no evidence of vascularization/deposits/scarring. Intraocular pressure and fundus examination were normal in both eyes. Further systemic evaluation showed increased triglycerides, low high-density lipoprotein, anemia, and proteinuria with elevated renal parameters. Renal biopsy showed secondary membranous nephropathy arising in a background of lecithin cholesterol acyltransferase (LCAT) deficiency. Severe visual impairment prompts keratoplasty in such patients. Bilateral stromal corneal clouding is important to detect potentially associated systemic diseases such as mucopolysaccharidosis/lipidosis, LCAT deficiency, fish-eye disease, and corneal dystrophy. The case is being reported to stress the importance of systemic evaluation and follow-up in a case of bilateral corneal clouding due to its varied systemic differentials.
Keywords: Corneal clouding, lecithin cholesterol acyltransferase deficiency, lipoprotein disorder
|How to cite this article:|
Maheshwari S U, Muthayya M, Thiyagarajan P, Barathi G. Bilateral corneal clouding of lecithin cholesterol acyltransferase deficiency – A rare case report. TNOA J Ophthalmic Sci Res 2021;59:178-80
|How to cite this URL:|
Maheshwari S U, Muthayya M, Thiyagarajan P, Barathi G. Bilateral corneal clouding of lecithin cholesterol acyltransferase deficiency – A rare case report. TNOA J Ophthalmic Sci Res [serial online] 2021 [cited 2021 Jul 27];59:178-80. Available from: https://www.tnoajosr.com/text.asp?2021/59/2/178/319280
| Introduction|| |
Lecithin cholesterol acyltransferase (LCAT) deficiency is a rare genetic lipoprotein metabolism disorder. It is an autosomal recessive disorder caused by a mutation of LCAT gene located on chromosome 16 (16q22.1), which encodes the LCAT enzyme involved in reverse cholesterol transport from the peripheral tissues to the liver. LCAT deficiency impairs the esterification of free cholesterol in the plasma, leading to accumulation of phospholipids, in various organs, clinically characterized by corneal clouding, renal failure, and hemolytic anemia, as well as biochemically by severely reduced high-density lipoprotein (HDL) cholesterol. There are two forms of the disease: familial LCAT deficiency (FLD) in which there is complete LCAT deficiency and fish-eye disease in which there is a partial LCAT deficiency.
| Case Report|| |
A 44-year-old female came to our department with complaints of haziness of both corneas since childhood associated with gradual diminution of vision. No history of any ocular trauma, ocular surgery, and chronic drug usage in the past was noted. A positive family history of similar complaint was elicited [Figure 1]. On general examination, the patient was found to have mild pallor and bilateral pitting pedal edema. Blood pressure recorded was 150/90 mmHg. Her visual acuity was 6/12 with pinhole 6/9, near vision N12, following refraction best-corrected visual acuity improved to 6/9, N6 (±1.50 DC ×90 with +1.50 DS presbyopia correction) in both eyes. Ocular examination using slit lamp showed bilateral diffuse stromal corneal haze more prominent around the limbus with no evidence of aany vascularization/deposits/scarring [Figure 2] and [Figure 3]. Intraocular pressure and dilated fundus examination were normal in both eyes. Keraometry values in the right and left eye were as follows: (RE -K1:45.50, K2:47.00) and (LE -K1:45.00, K2:46.50) Central corneal thickness was slightly increased in both eyes (OD: 568 μm and OS: 572 μm).
|Figure 2: Right eye gross picture showing bilateral stromal corneal clouding|
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|Figure 3: Left eye gross picture showing bilateral stromal corneal clouding|
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The patient was referred to a physician for further systemic evaluation. The patient was found to be anemic (hemoglobin 7.9 gm%), and peripheral smear showed normocytic normochromic anemia. She also had elevated renal parameters (urea: 20 mg/dl, creatinine: 2.2 mg/dl), nephrotic range proteinuria, and abnormal fasting lipid profile which showed decreased HDL levels (35 mg/dl) and increased very low-density lipoprotein (40 mg/dl) and triglycerides levels (350 mg/dl). Plasma LCAT enzyme activity was markedly reduced. In view of elevated renal parameters, renal biopsy was done, which showed mesangial expansion and glomerular basement membrane thickening noted in the peripheral capillary loops with occasional vacuolization, which represents LCAT deficiency glomerulonephritis [Figure 4].
|Figure 4: Renal biopsy showing mesangial expansion and glomerular basement membrane thickening noted in the peripheral capillary loops with occasional vacuolization|
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The patient underwent complete refraction, following which best glasses were prescribed and advised annual ophthalmic follow-up. The patient was otherwise conservatively managed with low-fat, low-salt, and iron-rich diet. Renal parameters were monitored regularly. Angiotensin-converting-enzyme (ACE) inhibitors and antilipidemic drugs were commenced according to the physician's advice.
| Discussion|| |
LCAT deficiency is an autosomal recessive disorder characterized by a mutation in the gene located on 16q22.1, which encodes the LCAT enzyme that catalyzes the formation of cholesterol esters in lipoproteins. This mutation causes either complete or partial deficiency of enzyme activity, which leads to the accumulation of fat deposits in body tissues such as cornea, red blood cells (RBCs), and kidneys. The disorder is characterized clinically by corneal clouding, hemolytic anemia, proteinuria, and renal dysfunction. It has a prevalence of <1:1,000,000. LCAT is an enzyme that is expressed primarily in the liver and secreted into the plasma compartment. It causes esterification of free cholesterol in lipoproteins, leading to maturation of HDL that helps in reverse cholesterol transport. The disease has two forms.
- FLD: Caused by complete lack of alpha- and beta-LCAT enzyme activity, clinically characterized by corneal clouding, anemia, and renal insufficiency
- Fish-eye disease: There is loss of alpha-LCAT activity while the beta-LCAT activity is preserved, characterized only by corneal clouding, sometimes atherosclerosis.
Lipid deposition in the cornea is responsible for the corneal clouding. It consists of numerous, minute, grayish dot-like opacities forming a mosaic pattern, scattered throughout the corneal stroma, especially prominent near the limbal area, resembling arcus senilis. Corneal opacities usually appear early in life and gradually progress over time, constituting the first noticeable sign of the disease in the majority of patients. On slit-lamp examination of the cornea, the lipid dots can be seen in all layers of the corneal parenchyma. Light microscopy shows numerous small vacuoles dispersed in all the histological layers of the cornea but most densely in the anterior stroma; on electron microscopic study, some of these vacuoles contain electron-dense material.
Normocytic normochromic hemolytic anemia, characteristically of low clinical severity, is caused by deposition of free cholesterol and phosphatidylcholine in the membrane of the RBC, shortening their lifespan.
Chronic kidney disease is the principal cause of morbidity and mortality in patients with FLD. These patients have progressive proteinuria and renal impairment, leading to end-stage renal disease (ESRD) by 4th–5th decade of life. The pathogenesis of renal disease is not entirely understood; it has been suggested that LDL particles trapped in the capillary loops may trigger endothelial and vascular injury.
Currently, there is no causal treatment for FLD. Dietary modifications such as low-fat and low-salt diet are advised. Lipid-lowering therapy along with antihypertensive medication (ACE inhibitors) remains the mainstay of management; this combination has proven to retard the progression of the disease. The potential benefits of corticosteroid treatment have also been described. In ESRD, renal transplantation remains a viable option despite recurrences. The corneal opacification may be severe enough to cause visual impairment, sometimes requiring keratoplasty. Potential therapy with LCAT gene replacement and enzyme replacement is being explored. In one study, LCAT activity in the plasma was restored using autologous adipocytes transfected with human LCAT via a retroviral vector. Recombinant human LCAT (ACP-501) demonstrated favorable results in LCAT-knockout mice restoring LCAT activity, cholesterol efflux, and lipid profiles. Recombinant human LCAT evaluated in FLD patients in a phase 1 trial showed positive results and has given way to the ongoing clinical development of ACP-501.
| Conclusion|| |
Bilateral stromal corneal clouding is important to detect potentially associated systemic diseases such as mucopolysaccharidosis/lipidosis, LCAT deficiency, fish-eye disease, and corneal dystrophy. The case is being reported for its rarity and to stress the importance of systemic evaluation and follow-up in a case of bilateral stromal corneal clouding, due to its varied systemic differentials. Early ophthalmic evaluation prompts specific diagnosis and treatment.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]