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Bilateral Optic Atrophy in an Adolescent Male Patient

Educational Objective
Based on this clinical scenario and the accompanying image, understand how to arrive at a correct diagnosis.
1 Credit CME

A boy in his late teens with short stature presented with gradual loss of vision in both eyes since 8 years of age. He received a diagnosis of type 1 diabetes at 10 years of age and has been taking insulin since the diagnosis. He had consulted several physicians for hearing loss during the past 2 years. He had received multiple courses of antibiotics for frequent urinary tract infections. The results of a systemic examination revealed hypochondroplasia, alopecia (Figure 1), and generalized hypotonia. His best-corrected visual acuity was 6/60 OU. Bjerrum tangent screen visual field analysis showed preservation of central 10 degrees of fields. His color vision was defective, and his pupils were slow reactive to light. The results of an optic nerve examination revealed bilateral pale optic discs with no evidence of edema and normal retinal vasculature. The results of the examination of the macula were normal in both eyes, with no diabetic retinopathy. A urine specific gravity test was performed, and the urine specific gravity was found to be low (sp g 1.001-1.003), consistent with diabetes insipidus.

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Wolfram disease (DIDMOAD [diabetes insipidus, diabetes mellitus, optic atrophy, and deafness] syndrome)

B. Order a hormone profile (thyrotropin, adrenocorticotrophic hormone, growth hormone, and testosterone) and consult endocrinology

This is a case of an adolescent boy with bilateral optic atrophy (Figure 2). The differential diagnosis includes hereditary optic neuropathies such as Leber optic neuropathy, autosomal dominant optic atrophy, and Wolfram disease1; compressive tumors; and traumatic and toxic neuropathy. Systemic involvement including bilateral sensorineural deafness, diabetes mellitus, and diabetes insipidus led us to the diagnosis of DIDMOAD syndrome.

Wolfram disease is also called DIDMOAD syndrome, an eponym for diabetes insipidus, diabetes mellitus, optic atrophy, and deafness. The initial manifestation is insulin-dependent diabetes mellitus around 6 years of age, followed by optic atrophy at 11 years of age.2 In the second decade, many patients develop diabetes insipidus and sensorineural deafness. Inheritance is autosomal recessive and is due to mutations in the WFS1 gene in the short arm of chromosome 4 that encodes transmembrane proteins in endoplasmic reticulum, thus resulting in a multi-organ system disorder.3

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Article Information

Corresponding Author: Priya Sivakumar, MS, Department of Neuro-ophthalmology, Aravind Eye Care, B-11, Thavalakuppam Pondicherry, India 605007 (priya86sundaralakshmi@gmail.com).

Published Online: October 25, 2018. doi:10.1001/jamaophthalmol.2018.2594

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

Additional Contributions: We thank the patient for granting permission to publish this information.

References
1.
Biousse  V, Newman  NJ.  Hereditary optic neuropathies.  Ophthalmol Clin North Am. 2001;14(3):547-568.PubMedGoogle ScholarCrossref
2.
Barrett  TG, Bundey  SE, Macleod  AF.  Neurodegeneration and diabetes.  Lancet. 1995;346(8988):1458-1463.PubMedGoogle ScholarCrossref
3.
Collier  DA, Barrett  TG, Curtis  D,  et al.  Linkage of Wolfram syndrome to chromosome 4p16.1 and evidence for heterogeneity.  Am J Hum Genet. 1996;59(4):855-863.PubMedGoogle Scholar
4.
Kinsley  BT, Swift  M, Dumont  RH, Swift  RG.  Morbidity and mortality in the Wolfram syndrome.  Diabetes Care. 1995;18(12):1566-1570.PubMedGoogle ScholarCrossref
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Ito  S, Sakakibara  R, Hattori  T.  Wolfram syndrome presenting marked brain MR imaging abnormalities with few neurologic abnormalities.  AJNR Am J Neuroradiol. 2007;28(2):305-306.PubMedGoogle Scholar
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Urano  F.  Wolfram syndrome: diagnosis, management, and treatment.  Curr Diab Rep. 2016;16(1):6.PubMedGoogle ScholarCrossref
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Borgna-Pignatti  C, Marradi  P, Pinelli  L, Monetti  N, Patrini  C.  Thiamine-responsive anemia in DIDMOAD syndrome.  J Pediatr. 1989;114(3):405-410.PubMedGoogle ScholarCrossref
8.
Hansen  L, Eiberg  H, Barrett  T,  et al.  Mutation analysis of the WFS1 gene in seven Danish Wolfram syndrome families.  Eur J Hum Genet. 2005;13(12):1275-1284.PubMedGoogle ScholarCrossref
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