Summary

Wolfram syndrome (WS) is the inherited association of juvenile-onset insulin-dependent diabetes mellitus and progressive bilateral optic atrophy. We have identified a complete DIDMOAD syndrome. Bilateral papillary atrophy was found in optic fundoscopic examination. The diagnosis of diabetes insipidus was determined after a water deprivation test. Fasting serum insulin levels was 0.4uU/ml and serum C-peptide level was 0.2 ng/ml. Antibodies to islet cell (ICA) and anti-insulin antibodies were negative. In MRI of the patient the posterior pituitary bright spot was absent. Deafness was found in odiometric examination. The disease is believed to account for 1/150 patients with young-onset insulin-requiring diabetes mellitus. Interestingly we follow- up almost 450 patients with type 1 diabetes mellitus per year, but we determined a Wolfram syndrome at first time. In the literature WS were found 27 patients in 589 type 1 diabetic patients. Whereas in UK population syndrome is rare and its prevalence is estimated to be 1/ 770 000 people. As a result we can say that frequency of syndrome may show ethnic differences and may be rare in our region.
Keywords: Wolfram syndrome, optic atrophy, diabetes mellitus, diebetes insipidus and deafness

Introduction

Wolfram syndrome (WFS) was first described in 1938 as a combination of familial juvenile-onset diabetes mellitus and optic atrophy. Insulin-requiring diabetes mellitus occurs with mean age of onset at 6 years [1]. When examined, pancreatic islets were atrophic and insulin-producing (beta)-cells selectively absent. The disease is believed to account for 1/150 patients with young-onset insulin-requiring diabetes mellitus [1]. The pathogenesis of Wolfram syndrome is unknown. Linkage of the gene to markers on chromosome 4p was reported in 1994 and recently were determined successful in the positional cloning of the WFS gene (WFS1) [2]. But in a recent study Tanizawa [3] has shown the gene within a region less than 250 kb on chromosome 6p. In the region, it was identified a novel gene (WFS1) encoding a putative trans-membrane protein. Comparison of the cDNA sequence of WFS1 with those in public databases revealed no related genes.

Case Presentation

(File no: 517178 and protocol no: 1996063981), HB, A 16-year-old girl (height, 138 cm (-4 SD) body weight, 27 kg, BMI: 14 kg/m2) was presented with diabetes mellitus and optic atrophy (Figure 1). Her parents and siblings did not have diabetes mellitus. Diabetes mellitus had appeared who she was 8 year old. Before admitted to our department, she has been treated with diet and insulin since 1993. At first her fasting serum insulin levels was 0.4 U/ml (normal: 3-17 U/ml) and serum Cpeptide level was 0.2 ng/ml (reference range <3.5 ng/ml). After strict glycemic control for three months, we performed an oral glucose tolerance test with 48-gram glucose (1.75 gr/per body weight). Insulin concentrations at basal, 30th, 60th, 90th, 120th minutes were 0.4 U/ml, 0.5 U/ml, 0.6 U/ml, 0.5 U/ml, 0.4 U/ml respectively. After glucose loading, C-peptide levels were found to be 0.2 ng/ml, 0.3 ng/ml, 0.2 ng/ml, 0.2 ng/ml, 0.3 ng/ml respectively. The results of laboratory investigations, including liver and renal function tests and measurement of serum lactate and pyruvate levels, were within normal ranges. Islet cell antibodies (ICA) was 1.8 JDF unit (reference range <5 unit) and anti-insulin antibodies was 0.2 KronusU/ml (reference range <1.0 s U/ml) detected as negative. In optic fundoscopic examination, bilateral papillary atrophy, diffuse narrowing in retinal arteries, and grade-1 hypertensive retinopathy were found. The patient has been suffering from blurred vision and polyuria. The diagnosis of diabetes insipidus was determined after a water deprivation test. Before water deprivation test plasma osmolality of the patient was 314 mosm/ kg and urine osmolality was 200 mosm/L. During the test tension arterial, urine volume, body weight, plasma and urine osmolality were measured. Water deprivation test was terminated at end of 6th hour, because of the fact that body weight falls by more than 3%. At the end of the test plasma osmolality was 319 mosm/ kg and urine osmolality was 205 mosm/L. Vasopressin levels was 1 pg/ml (reference range 0-14 pg/ml). Then, desmopressin acetate was administrated subcutaneously, after one-hour, urine osmolality increased to 325 mosm/L. As a result, patient was accepted as central type diabetes insipitus. Other basal hypophyseal hormone levels were within normal limits. In MRI of the patient the posterior pituitary bright spot, which is normally visualized by MRI, was absent in the patient. Urinary tract dilatation and bladder dysfunction are coexisting features of this syndrome [4]. However no signs of urinary tract dilatation was revealed by ultrasonography. Diverse and serious psychiatric manifestations frequently have been observed in wolfram syndrome [1,5]. But, our patient was found as normal by psychiatric evaluation. HLA-DR2 haplotype has been reported to be associated with wolfram syndrome. But, we could not studied HLA subgroups because of technical failure [6]. Neurosensory hearing lost was found in odiometric examination of the patient. Other coexisting features of DIDMOAD syndrome, such as cerebellar atrophy, were not found. The patient's diabetes mellitus was not well controlled (glycosylated hemoglobin (HbA1c: 12.4 %) [Reference range, 4- 6%]). Three-daily administration of regular insulin and bedtime NPH insulin were given for the treatment of diabetes mellitus. For the treatment of diabetes insipidus, Desmopressin acetate was given at the dose of 20 g/day by nasal route. She was not ketosis prone.

References

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