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Year : 2020  |  Volume : 8  |  Issue : 3  |  Page : 122-124

Wolfram syndrome with childhood glaucoma: A rare case report with review of literature

1 Department of Ophthalmology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
2 Department of Pediatrics, Mayo Institute of Medical Sciences, Barabanki, Uttar Pradesh, India

Date of Submission23-Mar-2020
Date of Decision04-Jul-2020
Date of Acceptance19-Oct-2020
Date of Web Publication4-Dec-2020

Correspondence Address:
Vaibhav Kumar Jain
Department of Ophthalmology, Sanjay Gandhi Post Graduate Institute of Medical Science, Raebareli Road, Lucknow, Uttar Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcor.jcor_26_20

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Wolfram syndrome (WFS) is a rare neurodegenerative disorder characterized by young-onset diabetes mellitus, central diabetes insipidus, optic nerve atrophy, and hearing loss. The ophthalmic association of this order has been limited to optic nerve atrophy. We report here a case of WFS and its disease course with childhood glaucoma as a rare ophthalmic manifestation which has been reported just once earlier. The patient had young-onset diabetes mellitus (insulin dependent), diabetes insipidus, and optic-disc pallor suggestive of partial optic atrophy. However, hearing assessment was normal at the time of presentation and in due course of disease. Glaucoma is one of the rare possible ocular manifestations of WFS which should be highly considered while evaluating patient with this disorder.

Keywords: Diabetes insipidus, diabetes mellitus, DIDMOAD syndrome, glaucoma, optic atrophy, Wolfram syndrome

How to cite this article:
Kesarwani D, Jain G, Sarswati, Agarwal R, Sharma K, Jain VK. Wolfram syndrome with childhood glaucoma: A rare case report with review of literature. J Clin Ophthalmol Res 2020;8:122-4

How to cite this URL:
Kesarwani D, Jain G, Sarswati, Agarwal R, Sharma K, Jain VK. Wolfram syndrome with childhood glaucoma: A rare case report with review of literature. J Clin Ophthalmol Res [serial online] 2020 [cited 2022 Jun 26];8:122-4. Available from: https://www.jcor.in/text.asp?2020/8/3/122/302196

Wolfram syndrome (WFS) is a progressive neurodegenerative disorder first described in 1938 by Wolfram and Wager.[1] It is inherited as autosomal-recessive syndrome characterized by early-onset diabetes mellitus, progressive optic atrophy in the 1st decade of life, cranial diabetes insipidus with sensorineural deafness in the 2nd decade of life, renal tract abnormalities in the 3rd decade, and multiple neurological abnormalities such as myoclonus and psychiatric illness in the 4th decade of life.[2] Considering these features, it is also known as DIDMOAD syndrome, acronym for diabetes insipidus diabetes mellitus, optic atrophy, and sensory neural deafness. It results from non-inflammatory atrophic changes in the brain and in pancreatic islets.

Affected patients have short life span, 3–4 decades resulting from central respiratory failure due to brainstem atrophy. Genetic studies have shown that there is the mutation of WFS1 gene on chromosome 4 (90%).[3] This gene encodes an endoplasmic reticulum membrane protein (Wolframin) found in neurons and pancreatic beta cells as well as other tissues including the heart, placenta, inner ear, lung, and liver. To date, function of putative protein remains unclear.

To the best of our knowledge, there has been only one report of developmental glaucoma associated with WFS.[4] Herein, we report this rare case of childhood glaucoma associated with WFS and describe the course of disease in this patient.

  Case Report Top

A 12-year-old boy who was a known case of WFS was referred for routine ophthalmic evaluation from the pediatric endocrinology department of our institute. His best-corrected visual acuity was 20/25 in both eyes with refractive correction of − 0.75DS–0.50DC × 130° in the right eye and − 0.50DS–0.50DC × 165° in the left eye. On measuring intraocular pressure (IOP) with Goldmann Applanation tonometry, the patient had 32 mm Hg in the right eye and 30 mm Hg in the left eye. Anterior segment examination revealed bilateral clear cornea, sluggish pupil reaction with no relative afferent pupillary defect, deep and quiet anterior chamber with clear lens. His fundus examination showed cup-disc ratio of 0.6 with temporal pallor in both eyes [Figure 1]. Gonioscopy revealed wide open angles with fine iris processes in both eyes. Central corneal thickness (SP-2000, Tomey, Nagoya, Japan) measurements were 651 and 596 microns, in the right eye and left eye, respectively. Visual field examination (Humphrey Field Analyzer, Carl Zeiss, Meditec, Inc.) showed early defects which was more on inferior field in both eyes [Figure 2]. On the basis of clinical examination, the diagnosis of childhood glaucoma associated with WFS was made. To control IOP in both eyes, timolol (0.5%) was started in both eyes with the target IOP in the range of higher teens. He was called after 4 weeks of therapy, but he reported after 8 weeks. His IOPs on timolol (30 mm Hg in the right eye and 28 mm Hg in the left eye) were uncontrolled in both eyes. Then, the patient was shifted to bimataprost (0.01%) at bed time. After 6 weeks, the patient had IOP of 18 mm Hg in both eyes, and medication was continued.
Figure 1: Fundus photographs of a patient with Wolfram syndrome showing cup-disc ratio of 0.6 and temporal disc pallor suggestive of partial optic nerve atrophy (right and left)

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Figure 2: Humphrey visual field print-out of patient with Wolfram syndrome showing early defects mostly in inferior half of the field (a) Right eye; (b) Left eye

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His past records showed that he presented to pediatric endocrinology outpatient department at the age of 4½ years with complaints of polyuria, polydipsia, and weight loss for the past 2 months. Capillary blood sugar by glucometer was 454 mg/dL, urine ketones were moderately positive, and venous blood gas did not show metabolic acidosis. Child was admitted and started on insulin with basal-bolus regimen. Routine investigations were sent which showed glycated hemoglobin 13.5%, thyroid-stimulating hormone 2.1 mIU/L, and anti endomysial antibodies negative. Total daily insulin requirement was around 1 unit/kg/day. Parents were counseled regarding insulin-dependent diabetes mellitus condition of their child and the need for life-long multiple daily injections of insulin and appropriate blood sugar monitoring at home with glucometer. Ambulatory diabetes management education was given to the parents, and the child was discharged. On follow-up, glycemic control was satisfactory but polyuria persisted. Polyuria was evaluated subsequently, and the child was found to have diabetes insipidus. Water deprivation test was done to rule out nephrogenic diabetes insipidus. A provisional diagnosis of WFS was made. Child did not have any sensorineural hearing loss or optic atrophy at that time.

After 2 years of an initial diagnosis of WFS, child started complaining of visual blurring in both eyes. On his subsequent follow-up in our hospital, he was referred to the ophthalmology department for proper evaluation. His refractive error was corrected with final visual acuity of 20/25 in both eyes. His IOPs were 14 mm Hg in both the eyes at that time. On fundus examination, he was found to have bilateral temporal disc pallor and an impression of bilateral partial optic atrophy was made, thus evolution of third cardinal feature of DIDMOAD syndrome. A hearing assessment was done again, but any evidence of sensorineural hearing loss was not found. No evidence either for any sensory or autonomic neuropathy. Family screening did not reveal any abnormality.

  Discussion Top

Classically, the ophthalmological association of WFS has been limited to optic nerve atrophy which is also one of the cardinal features to diagnose this disorder. However, retinal degeneration and congenital cataract have also been reported in this disorder.[5],[6] Bekir et al. were the first to report juvenile glaucoma and posterior polar cataract in one case and myopia in both cases of their series of two patients in a Turkish family.[4] In another case report, there have been association developmental glaucoma with central diabetes insipidus.[7] However, the absence of diabetes mellitus ruled out the possible WFS in their patient.

In our patient, diabetes mellitus, diabetes insipidus, and partial optic atrophy were the classical features present. Myopia and childhood glaucoma were the rare manifestations present in our case. IOP was controlled with one anti-glaucoma medication (bimataprost 0.01% once at bedtime) and did not required any further medication. Similarly, Bekir et al. also reported juvenile glaucoma which was controlled with one antiglaucoma medication (metipranolol 3% twice daily).[4] The sensorineural hearing loss, neurological and psychiatric manifestations, and urinary tract problems were not present in our case. These manifestations may develop later on the course of disease as the age increases.

This syndrome should be highly considered in young diabetic patients with high blood sugars presenting with unexplained visual loss or polyuria and polydipsia. Glaucoma is a rare possibility in cases of WFS that should be ruled out as a part of routine ocular examination in these cases.

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

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Conflicts of interest

There are no conflicts of interest.

  References Top

Wolfram DJ, Wagner HP. Diabetes mellitus and simple optic atrophy among siblings: Report of four cases. Mayo Clin Proc 1938;1:715-8.  Back to cited text no. 1
Barrett TG, Bundey SE, Macleod AF. Neurodegeneration and diabetes: UK nationwide study of Wolfram (DIDMOAD) syndrome. Lancet 1995;346:1458-63.  Back to cited text no. 2
Inoue H, Tanizawa Y, Wasson J, Behn P, Kalidas K, Bernal-Mizrachi E, et al. A gene encoding a transmembrane protein is mutated in patients with diabetes mellitus and optic atrophy (Wolfram syndrome). Nat Genet 1998;20:143-8.  Back to cited text no. 3
Bekir NA, Güngör K, Güran S. A DIDMOAD syndrome family with juvenile glaucoma and myopia findings. Acta Ophthalmol Scand 2000;78:480-2.  Back to cited text no. 4
Scaramuzzi M, Kumar P, Peachey N, Nucci P, Traboulsi EI. Evidence of retinal degeneration in Wolfram syndrome. Ophthalmic Genet 2019;40:34-8.  Back to cited text no. 5
Mets RB, Emery SB, Lesperance MM, Mets MB. Congenital cataracts in two siblings with Wolfram syndrome. Ophthalmic Genet 2010;31:227-9.  Back to cited text no. 6
Ramawant PK, Dewan T, Vashisht S, Chawla H, Kapoor K, Saha A, et al. Developmental glaucoma with central diabetes insipidus: A case report and review of literature. Delhi J Ophthalmol 2016;27:35-7.  Back to cited text no. 7


  [Figure 1], [Figure 2]


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