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Table of Contents
CASE REPORT WITH REVIEW OF LITERATURE
Year : 2013  |  Volume : 17  |  Issue : 5  |  Page : 920-921

A young diabetic with suicidal risk: Rare disease with a rarer presentation


Department of Endocrinology, LLRM Medical College Campus, Meerut, Uttar Pradesh, India

Date of Web Publication29-Aug-2013

Correspondence Address:
Rajeev Philip
G10, PG Hostel, LLRM Medical College Campus, Garh Road, Meerut, Uttar Pradesh - 250 004
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2230-8210.117218

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   Abstract 

Rare genetic or inherited forms of diabetes can mimic immune mediated type 1 diabetes. Early age of onset and associated features help to differentiate these diseases from type 1 diabetes. Wolfram syndrome, an inherited neuro degenerative disorder, presents as insulin dependent diabetes mellitus, diabetes insipidus, optic atrophy and deafness. But less well described features like psychiatric manifestations can be the presentation of this disease. We present such a case. Wolfram syndrome should be considered as a differential diagnosis in insulin dependent diabetic children who present with neuropsychiatric problems.

Keywords: Diabetes in young, neuropsychiatric manifestations, wolfram syndrome


How to cite this article:
Philip R, Patidar P P, Agarwal P, Gupta K K. A young diabetic with suicidal risk: Rare disease with a rarer presentation. Indian J Endocr Metab 2013;17:920-1

How to cite this URL:
Philip R, Patidar P P, Agarwal P, Gupta K K. A young diabetic with suicidal risk: Rare disease with a rarer presentation. Indian J Endocr Metab [serial online] 2013 [cited 2019 Aug 22];17:920-1. Available from: http://www.ijem.in/text.asp?2013/17/5/920/117218


   Introduction Top


Rare genetic or sporadic forms of diabetes can present as insulin dependent diabetes in children and can mimic type 1 diabetes. Very early onset of symptoms and associated features help in differentiating these forms of diabetes from type 1 diabetes. [1] One of the rare forms of diabetes is Wolfram syndrome, which is an inherited or sporadic neuro degenerative disorder, presenting as, diabetes insipidus, diabetes mellitus, optic atrophy and deafness (DIDMOAD). But there are less well known manifestations of this syndrome, which include neuropsychiatric manifestations, reproductive abnormalities, limited joint mobility, cardiovascular and gastrointestinal autonomic neuropathy, any of which can be the presenting feature. [2],[3],[4] We report a case of Wolfram syndrome, whose presentation was of severe depression with suicidal risk. Truly, a rare disease with a rarer presentation.


   Case Report Top


A 15 year diabetic boy was admitted in our hospital for evaluation of behavioural problems. He was diagnosed to have diabetes at the age of 4 years, and was on thrice daily pre mix insulin. His current problem was severe depressive symptoms for the past 5 years. He also had history of temper tantrums, with frequent fights with his classmates over minor issues. Off late, he had become very aloof, with decreasing peer interactions and strained relations with his parents. His scholastic performance had also declined significantly. He also had history of decreased vision for the past 4 years, and decreased hearing for the past 2 years. His glycemic control was good till six months back, but recently had widely fluctuating blood glucose, with the last two/HbA1c levels above target.

Examination revealed that he had significant loss of vision, with 6/24 vision in both eyes. Fundoscopy was suggestive of optic atrophy [Figure 1]. An audiometry revealed significant sensory neural hearing loss, especially at the higher frequencies. A 24 hour urine output was measured after control of blood sugars, which was 4.1 litres, indicating polyuria. The serum osmolality was high?305 mOsm/kg-305 mOsm/kg (corresponding blood glucose 147 mg/dl) and urine osmolality was low (168 mOsm/kg), and serum sodium was 146 meq/l, suggestive of diabetes insipidus. MRI of the brain was done, which showed altered signal intensity at the optic nerve, absent posterior pituitary bright spot in T1 (suggestive of central diabetes insipidus), with atrophy of the brainstem [Figure 2]. Based on these findings-DIDMOAD and psychiatric manifestations, the final diagnosis of Wolfram syndrome was made.
Figure 1: Fundus photograph showing optic atrophy

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Figure 2: MRI brain (T1) showing absent bright spot of posterior pituitary (small arrow) and brainstem atrophy (big arrow)

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   Discussion Top


Wolfram syndrome is a rare neuro degenerative disorder which may be autosomal recessively inherited or may be sporadic. First described in 1938 by Wolfram and Wagener, Wolfram syndrome manifests as a combination of young onset non-immune insulin dependent diabetes mellitus and progressive optic atrophy in all patients with added diabetes insipidus and sensory neural deafness in 70% of the patients and hence referred as DIDMOAD syndrome. [5]

The syndrome is due to the defective synthesis of wolframin, (a 100-kd transmembrane protein encoded by WFS1, a gene located at 4p16.1.116) found in the endoplasmic reticulum and in the neuronal and neuroendocrine tissues. Wolframin induces ion channel activity with a resultant increase in intracellular calcium and may play an important role in intracellular calcium homeostasis. [6]

Due to variable expression of the protein, the phenotype of the disease varies, with diabetes mellitus manifesting early followed by optic atrophy in all the patients. Other manifestations like diabetes insipidus, deafness, neurologic manifestations, other hormonal deficiencies like ACTH deficiency and growth hormone deficiency, thiamine responsive sideroblastic anaemia, have variable penetrance. [7]

Psychiatric manifestations of Wolfram syndrome occur less commonly and are less well documented. Upto 22% of patients can have psychiatric problems, based on different series. The major manifestations include severe depression, suicidal risk, poor scholastic performance, temper tantrums and adjustment disorder. [7],[8] Moreover, heterozygous carriers of the gene for Wolfram syndrome, who constitute about 1% of the general population are at a higher risk of developing psychiatric illness and have a 26 fold more chance of having a psychiatric hospitalisation. [9]

Our case is unique in the aspect that the psychiatric manifestations were the presenting feature, which lead to the diagnosis of the disease. This also brings to light the less talked about neuropsychiatric problems associated with Wolfram syndrome, and gives the message that Wolfram syndrome should be considered as a differential diagnosis in insulin dependent diabetic children who present with neuropsychiatric problems.

 
   References Top

1.Chan M, Rewers M. Diabetes in childhood. In: Holt R, Cockram C, editors. Textbook of diabetes. 4 th ed. USA: Blackwell Publishing; 2010.  Back to cited text no. 1
    
2.Tekgül S, Oge O, Simºek E, Yordam N, Kendi S. Urological manifestations of the Wolfram syndrome: Observations in 14 patients. J Urol 1999;161:616-7.  Back to cited text no. 2
    
3.Grosse Aldenhövel HB, Gallenkamp U, Sulemana CA. Juvenile onset diabetes mellitus, central diabetes insipidus and optic atrophy (Wolfram syndrome): Neurological findings and prognostic implications. Neuropediatrics 1991;22:103-6.  Back to cited text no. 3
    
4.Swift RG, Perkins DO, Chase CL, Sadler DB, Swift M. Psychiatric disorders in 36 families with Wolfram syndrome. Am J Psychiatry 1991;148:775-9.  Back to cited text no. 4
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5.Wolfram DJ. Diabetes mellitus and simple optic atrophy among siblings: Report of four cases. Mayo Clin Proc 1938;9:715-8.  Back to cited text no. 5
    
6.Osman AA, Saito M, Makepeace C, Permutt MA, Schlesinger P, Mueckler M. Wolframin expression induces novel ion channel activity in endoplasmic reticulum membranes and increases intracellular calcium. J Biol Chem 2003;278:52755-62.  Back to cited text no. 6
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7.Medlej R, Wasson J, Baz P, Azar S, Salti I, Loiselet J, et al. Diabetes mellitus and optic atrophy: A study of Wolfram syndrome in the Lebanese population. J Clin Endocrinol Metab 2004;89:1656-61.  Back to cited text no. 7
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8.Barrett TG, Bundey SE, Macleod AF. Neurodegeneration and diabetes: UK nationwide study of Wolfram syndrome. Lancet 1995;346:1458-63.  Back to cited text no. 8
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9.Swift M, Swift RG. Psychiatric disorders and mutations at the Wolfram syndrome locus. Biol Psychiatry 2000;47:787-93.  Back to cited text no. 9
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    Figures

  [Figure 1], [Figure 2]



 

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