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. 2015 Jun;6(7):1-5.
doi: 10.4172/2155-6156.1000561.

A Challenging Form of Non-autoimmune Insulin-Dependent Diabetes in a Wolfram Syndrome Patient with a Novel Sequence Variant

Liliana P Paris  1 , Yoshihiko Usui  1 , Josefina Serino  2 , Joaquim Sá  3 , Martin Friedlander  1
Affiliations

A Challenging Form of Non-autoimmune Insulin-Dependent Diabetes in a Wolfram Syndrome Patient with a Novel Sequence Variant

Liliana P Paris et al. J Diabetes Metab. 2015 Jun.

Abstract

Wolfram syndrome type 1 is a rare, autosomal recessive, neurodegenerative disorder that is diagnosed when insulin-dependent diabetes of non-auto-immune origin and optic atrophy are concomitantly present. Wolfram syndrome is also designated by DIDMOAD that stands for its most frequent manifestations: diabetes insipidus, diabetes mellitus, optic atrophy and deafness. With disease progression, patients also commonly develop severe neurological and genito-urinary tract abnormalities. When compared to the general type 1 diabetic population, patients with Wolfram Syndrome have been reported to have a form of diabetes that is more easily controlled and with less microvascular complications, such as diabetic retinopathy. We report a case of Wolfram syndrome in a 16-year-old male patient who presented with progressive optic atrophy and severe diabetes with very challenging glycemic control despite intensive therapy since diagnosis at the age of 6. Despite inadequate metabolic control he did not develop any diabetic microvascular complications during the 10-year follow-up period. To further investigate potential causes for this metabolic idiosyncrasy, we performed genetic analyses that revealed a novel combination of homozygous sequence variants that are likely the cause of the syndrome in this family. The identified genotype included a novel sequence variant in the Wolfram syndrome type 1 gene along with a previously described one, which had initially been associated with isolated low frequency sensorineural hearing loss (LFSNHL). Interestingly, our patient did not show any abnormal findings with audiometry testing.

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Figures

Figure 1
Figure 1
Retinographies at age 10 (A) and at age 16 (B), showing severe optic atrophy with no retinal changes suggestive of diabetic retinopathy. RE = right eye; LE: left eye.
Figure 2
Figure 2
Segregation of the WFS1 gene variants (c1066T>C and c482G>A) in the nuclear family of the patient.
See this image and copyright information in PMC

References

    1. Hansen L, Eiberg H, Barrett T, Bek T, Kjaersgaard P, et al. Mutation analysis of the WFS1 gene in seven Danish Wolfram syndrome families; four new mutations identified. Eur J Hum Genet. 2005;13:1275–1284. - PubMed
    1. Marshall BA, Permutt MA, Paciorkowski AR, Hoekel J, Karzon R, et al. Phenotypic characteristics of early Wolfram syndrome. Orphanet J Rare Dis. 2013;8:64. - PMC - PubMed
    1. Yu G, Yu ML, Wang JF, Gao CR, Chen ZJ. WS1 gene mutation analysis of Wolfram syndrome in a Chinese patient and a systematic review of literatures. Endocrine. 2010;38:147–152. - PubMed
    1. Barrett TG, Bundey SE, Macleod AF. Neurodegeneration and diabetes: UK nationwide study of Wolfram (DIDMOAD) syndrome. Lancet. 1995;346:1458–1463. - PubMed
    1. Homa K, Stefanski A, Zmyslowska A, Moleda P, Bryskiewicz ME, et al. False diagnosis of type 1 diabetes mellitus and its complications in Wolfram syndrome--is it the reason for the low number of reported cases of this abnormality? Endokrynol Pol. 2014;65:398–400. - PubMed

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