Endocrinol Metab.  2010 Jun;25(2):131-134. 10.3803/EnM.2010.25.2.131.

A Case of Wolfram Like Disorder with Type 2 Diabetes Mellitus in an Adult

• Choi SU
• Bae SK
• Kim HS
• Kim KR
• Hur KH
• Lim SH
• Hong YA
• Chung SC

• KMID: 2169019
• DOI: http://doi.org/10.3803/EnM.2010.25.2.131

Abstract

Wolfram-like disorder is one of the WFS1-related disorders that are caused by mutation of the WFS1 genes. WFS1-related disorders are classified as Wolfram syndrome, Wolfram like disorder and nonsyndromic low-frequency sensorineural hearing loss (DFNA6/14/38). Wolfram syndrome is known to DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy and deafness), and it is an autosomal-recessive disorder that predisposes a patient to developing type 1 diabetes in association with progressive optic atrophy, and the disease shows various phenotypes. Wolfram like disorder is an autosomal-dominant disorder that predisposes a patient to develop type 2 diabetes in association with optic atrophy and hearing impairment. We experienced a case of Wolfram like disorder with diabetes, optic atrophy and sensorineural hearing loss in a 28-year-old woman who was admitted to our hospital. Our case demonstrated the E737K missense mutation on the WFS1 gene, which has been previously reported in the medical literature. The diagnosis of WFS1-related disorder was confirmed by the clinical features and molecular genetic testing of the WFS1 gene.

Keyword

Wolfram like disorder; WFS1-related disorder; Wolfram syndrome

MeSH Terms

Adult
Diabetes Mellitus
Diabetes Mellitus, Type 2
Female
Hearing Loss
Hearing Loss, Sensorineural
Humans
Molecular Biology
Mutation, Missense
Optic Atrophy
Phenotype
Tungsten
Wolfram Syndrome
Tungsten

Figure

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  Fig. 1 Pedigree of the family, arrow indicates patients.

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  Fig. 2 Result of direct sequencing of genomic DNA in WFS1 gene of our patient, direct sequencing reveals G to L mutation at nucleotide 2209 in 737 codon.

Reference

1. Wolfram DJ, Wagener HP. Diabetes mellitus and simple optic atrophy among siblings. Mayo Clin Proc. 1938. 13:715–718.

2. Blasi C, Pierelli F, Rispoli E, Saponara M, Vingolo E, Andreani D. Wolfram's syndrome: a clinical, diagnostic, and interpretative contribution. Diabetes Care. 1986. 9:521–528.

3. Riggs AC, Bernal-Mizrachi E, Ohsugi M, Wasson J, Fatrai S, Welling C, Murray J, Schmidt RE, Herrera PL, Permutt MA. Mice conditionally lacking the Wolfram gene in pancreatic islet beta cells exhibit diabetes as a result of enhanced endoplasmic reticulum stress and apoptosis. Diabetologia. 2005. 48:2313–2321.

4. Gomez-Zaera M, Strom TM, Rodriguez B, Estivill X, Meitinger T, Nunes V. Presence of a major WFS1 mutation in Spanish Wolfram syndrome pedigree. Mol Genet Metab. 2001. 72:72–81.

5. Inoue H, Tanizawa Y, Wasson J, Behn P, Kalidas K, Bernal-Mizrachi E, Mueckler M, Marshall H, Donis-Keller H, Crock P, Rogers D, Mikuni M, Kumashiro H, Higashi K, Sobue G, Oka Y, Permutt MA. A gene encoding a transmembrane protein is mutated in patients with diabetes mellitus and optic atrophy (Wolfram syndrome). Nat Genet. 1998. 20:143–148.

6. Takeda K, Inoue H, Tanizawa Y, Matsuzaki Y, Oba J, Watanabe Y, Shinoda K, Oka Y. WFS1 (Wolfram syndrome 1) gene product: predominant subcellular localization to endoplasmic reticulum in cultured cells and neuronal expression in rat brain. Hum Mol Genet. 2001. 10:477–484.

7. Barrett TG, Bundey SE, Macleod AF. Neurodegeneration and diabetes: UK nationwide study of Wolfram (DIDMOAD) syndrome. Lancet. 1995. 346:1458–1463.

8. Karasik A, O'Hara C, Srikanta S, Swift M, Soeldner JS, Kahn CR, Herskowitz RD. Genetically programmed selective islet beta-cell loss in diabetic subjects with Wolfram's syndrome. Diabetes Care. 1989. 12:135–138.

9. Cano A, Molines L, Valéro R, Simonin G, Paquis-Flucklinger V, Vialettes B. French Group of Wolfram Syndrome. Microvascular diabetes complications in Wolfram syndrome (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness [DIDMOAM]): an age- and duration-matched comparison with common type 1 diabetes. Diabetes Care. 2007. 30:2327–2330.

10. Pennings RJ, Huygen PL, van den Ouweland JM, Cryns K, Dikkeschei LD, Van Camp G, Cremers CW. Sex-related hearing impairment in Wolfram syndrome patients identified by inactivating WFS1 mutations. Audiol Neurootol. 2004. 9:51–62.

11. Sequeira A, Kim C, Seguin M, Lesage A, Chawky N, Desautels A, Tousignant M, Vanier C, Lipp O, Benkelfat C, Rouleau G, Turecki G. Wolfram syndrome and suicide: evidence for a role of WFS1 in suicidal and impulsive behavior. Am J Med Genet B Neuropsychiatr Genet. 2003. 119B:108–113.

12. Garbreëls BA, Swaab DF, de Klejin DP, Dean A, Seidah NG, Van de Loo JW, Van de Ven WJ, Martens GJ, Van Leeuwen FW. The vasopressin precursor is not processed in the hypothalamus of Wolfram syndrome patients with diabetes insipidus: evidence for the involvement of PC2 and 7B2. J Clin Endocrinol Metab. 1998. 83:4026–4033.

13. Scolding NJ, Kellar-Wood HF, Shaw C, Shneerson JM, Antoun N. Wolfram syndrome: hereditary diabetes mellitus with brainstem and optic atrophy. Ann Neurol. 1996. 39:352–360.

14. Ohata T, Koizumi A, Kayo T, Shoji Y, Watanabe A, Monoh K, Higashi K, Ito S, Ogawa O, Wada Y, Takada G. Evidence of an increased risk of hearing loss in heterozygous carriers in a Wolfram syndrome family. Hum Genet. 1998. 103:470–474.

15. Swift RG, Polymeropoulos MH, Torres R, Swift M. Predisposition of Wolfram syndrome heterozygotes to psychiatric illness. Mol Psychiatry. 1998. 3:86–91.

16. Khanim F, Kirk J, Latif F, Barrett TG. WFS1/wolframin mutations, Wolfram syndrome, and associated diseases. Hum Mutat. 2001. 17:357–367.

17. Cryns K, Sivakumaran TA, Van den Ouweland JM, Pennings RJ, Cremers CW, Flothmann K, Young TL, Smith RJ, Lesperance MM, Van Camp G. Mutational spectrum of the WFS1 gene in Wolfram syndrome, nonsyndromic hearing impairment, diabetes mellitus, and psychiatric disease. Hum Mutat. 2003. 22:275–287.

18. Valéro R, Bannwarth S, Roman S, Paquis-Flucklinger V, Vialettes B. Autosomal dominant transmission of diabetes and congenital hearing impairment secondary to missense mutation in the WFS1 gene. Diabet Med. 2008. 25:657–661.

19. Eiberg H, Hansen L, Kjer B, Hansen T, Pedersen O, Bille M, Rosenberg T, Tranebjaerg L. Autosomal dominant optic atrophy associated with hearing impairment and impaired glucose regulation caused by a missense mutation in the WFS1 gene. J Med Genet. 2006. 43:435–440.

20. Ohtsuki T, Ishiguro H, Yoshikawa T, Arinami T. WFS1 gene mutation search in depressive patients: detection of five missense polymorphisms but no association with depression or bipolar affective disorder. J Affect Disord. 2000. 58:11–17.