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Wolfram syndrome: a clinicopathologic correlation

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Abstract

Wolfram syndrome or DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy and deafness) is a neurodegenerative disorder characterized by diabetes mellitus and optic atrophy as well as diabetes insipidus and deafness in many cases. We report the post-mortem neuropathologic findings of a patient with Wolfram syndrome and correlate them with his clinical presentation. In the hypothalamus, neurons in the paraventricular and supraoptic nuclei were markedly decreased and minimal neurohypophyseal tissue remained in the pituitary. The pontine base and inferior olivary nucleus showed gross shrinkage and neuron loss, while the cerebellum was relatively unaffected. The visual system had moderate to marked loss of retinal ganglion neurons, commensurate loss of myelinated axons in the optic nerve, chiasm and tract, and neuron loss in the lateral geniculate nucleus but preservation of the primary visual cortex. The patient’s inner ear showed loss of the organ of Corti in the basal turn of the cochleae and mild focal atrophy of the stria vascularis. These findings correlated well with the patient’s high-frequency hearing loss. The pathologic findings correlated closely with the patient’s clinical symptoms and further support the concept of Wolfram syndrome as a neurodegenerative disorder. Our findings extend prior neuropathologic reports of Wolfram syndrome by providing contributions to our understanding of eye, inner ear and olivopontine pathology in this disease.

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Acknowledgments

The authors would like to express their sincere thanks to the patient’s family for allowing us to conduct this study. We especially would like to thank the patient’s mother who has been of invaluable assistance in providing pertinent medical records and overall inspiration. Supported by NIH (U24 DC 008559), Mr. Lakshmi Mittal and Mr. Axel Eliasen.

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Authors and Affiliations

  1. Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave, Boston, MA, 02215, USA

    Justin B. Hilson

  2. Department of Otology and Laryngology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, USA

    Saumil N. Merchant & Joe C. Adams

  3. Department of Pathology, University of Calgary, Calgary, AB, Canada

    Jeffrey T. Joseph

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  1. Justin B. Hilson
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  2. Saumil N. Merchant
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Correspondence to Justin B. Hilson.

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Hilson, J.B., Merchant, S.N., Adams, J.C. et al. Wolfram syndrome: a clinicopathologic correlation. Acta Neuropathol 118, 415–428 (2009). https://doi.org/10.1007/s00401-009-0546-8

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  • DOI: https://doi.org/10.1007/s00401-009-0546-8

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