Ocular manifestations of homocystinuria due to cystathionine beta-synthase deficiency: A rare case report with genetic analysis

Damaris Magdalene; Ronel Soibam; Riddhi Raichura; Saurabh Deshmukh; Surpriya Hawaibam; Krati Gupta

doi:10.4103/tjosr.tjosr_86_20

CASE REPORT

Year : 2020 | Volume : 58 | Issue : 4 | Page : 302-303

Ocular manifestations of homocystinuria due to cystathionine beta-synthase deficiency: A rare case report with genetic analysis

Damaris Magdalene¹, Ronel Soibam², Riddhi Raichura³, Saurabh Deshmukh², Surpriya Hawaibam⁴, Krati Gupta³
¹ Department of Strabismus and Pediatric Ophthalmology, Sri Sankaradeva Nethralaya, Guwahati, Assam, India
² Department of Vitreo-Retina, Sri Sankaradeva Nethralaya, Guwahati, Assam, India
³ Department of Ophthalmology, Sri Sankaradeva Nethralaya, Guwahati, Assam, India
⁴ Department of Oculoplasty and Community Ophthalmology, Sri Sankaradeva Nethralaya, Guwahati, Assam, India

Date of Submission	10-Jul-2020
Date of Decision	02-Sep-2020
Date of Acceptance	04-Aug-2020
Date of Web Publication	16-Dec-2020

Correspondence Address:
Dr. Saurabh Deshmukh
Department of Vitreo.Retina, Sri Sankaradeva Nethralaya, Guwahati, Assam
India

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/tjosr.tjosr_86_20

Abstract

Microspherophakia is a developmental lens anomaly characterized by increased anteroposterior diameter and reduced equatorial diameter, which predisposes to secondary glaucoma. A 12-year-old boy presented with diminution of vision. Slit-lamp examination showed anteriorly dislocated crystalline lens. Blood analysis revealed elevated homocysteine levels. Genetic analysis showed cystathionine beta-synthase gene mutation, thus confirming the diagnosis of homocystinuria. To prevent secondary glaucoma, the patient was taken up for surgical intervention. This report highlights a case of homocystinuria with microspherophakia diagnosed with the help of genetic testing.

Keywords: Cystathionine beta-synthase, genetic analysis, homocystinuria, microspherophakia

How to cite this article:
Magdalene D, Soibam R, Raichura R, Deshmukh S, Hawaibam S, Gupta K. Ocular manifestations of homocystinuria due to cystathionine beta-synthase deficiency: A rare case report with genetic analysis. TNOA J Ophthalmic Sci Res 2020;58:302-3

How to cite this URL:
Magdalene D, Soibam R, Raichura R, Deshmukh S, Hawaibam S, Gupta K. Ocular manifestations of homocystinuria due to cystathionine beta-synthase deficiency: A rare case report with genetic analysis. TNOA J Ophthalmic Sci Res [serial online] 2020 [cited 2021 Jan 18];58:302-3. Available from: https://www.tnoajosr.com/text.asp?2020/58/4/302/303673

Introduction

Microspherophakia is a developmental abnormality of the crystalline lens characterized by increased anteroposterior diameter and reduced equatorial diameter.^[1] The inadequate force over the lens due to underdeveloped zonules of Zinn leads to microspherophakia.^[1] Faulty development of secondary lens fibers during embryogenesis is believed to be the pathophysiology of microspherophakia.^[2] Owing to the altered shape of the lens, patients usually have high myopia. They are also predisposed to lenticular dislocation and secondary angle closure glaucoma.^[3] Microspherophakia is usually associated with Weill–Marchesani syndrome, Marfan's syndrome, homocystinuria, hyperlysinemia, and congenital rubella.^[2] This report highlights a case of microspherophakia with crystalline lens dislocation diagnosed with the help of genetic testing.

Case Report

A 12-year-old boy presented with his mother with complaints of diminution of vision in both eyes (OU) since childhood. His mother gave a history of delayed milestone and mental retardation since childhood. On examination, his best-corrected visual acuity (BCVA) was 20/80, N12 (OU). His refractive error was -18.00/-1.50 × 10° in the right eye (OD) and -17.00/-1.75 × 170° in the left eye (OS). Slit-lamp examination showed anteriorly dislocated crystalline lens and vitreous in anterior chamber with circumciliary congestion congestion in OD [Figure 1]a. In OS, the entire lens equator was visualized with lax zonules [Figure 1]b. Intraocular pressure with applanation tonometer was 24 mmHg in OD and 16 mmHg in OS. Fundus examination was unremarkable, with the cup–disc ratio within normal limits in OU. The axial length of the eyes was 25.85 mm in OD and 26.03 mm in OS. Systemic evaluation did not show any abnormality. Blood sample for genetic analysis and urine sample for homocystinuria were sent for analysis. Blood analysis revealed elevated homocysteine (21.25 μmol/l). Genetic analysis showed homozygous missense variation in exon 5 of the cystathionine beta-synthase (CBS) gene (chr21:g. 44486374C > T; Depth: 32x) that results in the amino acid substitution of lysine for glutamic acid at codon 144 (p. Glu144 Lys; ENST00000398165.3), thus confirming the diagnosis of homocystinuria. Hence, to prevent further attack of secondary acute angle closure in OD, pars plana lensectomy was performed. In the left eye as well, to prevent pupillary block glaucoma, pars plana lensectomy was performed. The BCVA improved to 20/40, N6 OU.

Figure 1: Slit lamp photographs showing (a) anteriorly dislocated crystalline lens with circumciliary congestion in the right eye and (b) crystalline lens visible up to equator with lax zonules in the left

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Discussion

Microspherophakia is a rare bilateral condition characterized by small spherical lens as a result of lax zonules.^[4],[5] It has been reported in the literature to be associated with Weil–Marchesani syndrome, Marfan's syndrome, homocystinuria, and Alport's syndrome.^[5],[6] The atypical shape of the lens leads to complications such as pupillary block and secondary angle closure glaucoma.^[1],[2],[6]

Weil–Marchesani syndrome is a rare connective tissue disorder characterized by ocular and systemic manifestations. The systemic findings include brachydactyly and joint stiffness. The ocular findings are recognized in early childhood such as microspherophakia, myopia, ectopia lentis (either anteriorly or inferiorly), and secondary glaucoma. It either has autosomal dominant or recessive inheritance.^[7] Marfan's syndrome is another most commonly associated syndrome with microspherophakia. It is a connective tissue disorder characterized by a spectrum of ophthalmic and systemic findings. The ocular findings associated with Marfan's syndrome are ectopia lentis, severe myopia, microspherophakia, bluish discoloration of sclera, and retinal detachment may also be seen.^[4] CBS deficiency is autosomal recessive in nature and is characterized by homocystinuria and multisystemic involvement. For conversion of homocysteine to cystathionine, enzyme CBS is required. The clinical findings in a case of classic homocystinuria include developmental delay and mental retardation, ectopia lentis and/or severe myopia, microspherophakia, skeletal abnormalities, and thromboembolism.^[4]

Our patient presented with microspherophakia and anterior subluxation of lens. He was suspected to be affected with Marfan's syndrome or Weil–Marchesani syndrome. Detailed systemic examination and genetic testing ruled out Weil–Marchesani syndrome and Marfan's syndrome. The blood and genetic analysis of the patient confirmed the diagnosis of homocystinuria. As per the literature, occurrence of glaucoma is secondary. Eccentricity of the zonules from normal course of development can result in microspherophakia, which can further cause pupillary block glaucoma. Zonular integrity plays a major role in the predisposition to angle closure glaucoma. Loosened zonules can cause forward displacement of lens, which causes pupillary block and thus secondary angle closure glaucoma.^[1] Cycloplegics are first line of treatment. Procedures such as laser iridotomy and trabeculectomy are also considered beneficial in these patients. In patients with pupillary block and secondary glaucoma associated with microspherophakia, pars plana lensectomy is considered as a treatment modality.^[2],[6],[7] At presentation, our patient showed signs of secondary angle closure. Therefore, to prevent secondary glaucoma, the patient was taken up for surgical intervention. This case report highlights the unusual presentation of microspherophakia with crystalline lens dislocation and the use of genetic testing in a patient with homocystinuria.

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

Nil.

Conflicts of interest

There are no conflicts of interest.

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