|Year : 2016 | Volume
| Issue : 3 | Page : 229-231
Wolfram syndrome: A rare mimic of type 1 diabetes mellitus
Manish Gutch1, Krishna Kumar Sahani1, Annesh Bhattacharjee1, Sukriti Kumar2, Shobhit Shakya1
1 Department of Medicine, King George's Medical College, Lucknow, India
2 Department of Radiodiagnosis, King George's Medical College, Lucknow, India
|Date of Web Publication||9-Jun-2016|
Department of Medicine, King George's Medical College, Lucknow, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
Wolfram syndrome is a rare autosomal recessive disorder characterized by a constellation of disorders also known as diabetes insipidus, diabetes mellitus (DM), optic atrophy, and deafness. Patients present with DM and optic atrophy in the first decade, diabetes insipidus and sensorineural deafness in the second decade, and renal outflow tract anomalies and other neurological manifestations later in life. We report a case of a 14-year-old boy who was diagnosed with insulin-dependent DM and subsequently discovered to have optic atrophy, sensorineural hearing loss, and cardiovascular defect with a positive family history. Such cases need to be evaluated thoroughly with respect to Wolfram syndrome and its associated anomalies.
Keywords: Cardiovascular defect, neurological manifestations, type-1 diabetes mellitus, Wolfram syndrome
|How to cite this article:|
Gutch M, Sahani KK, Bhattacharjee A, Kumar S, Shakya S. Wolfram syndrome: A rare mimic of type 1 diabetes mellitus. CHRISMED J Health Res 2016;3:229-31
|How to cite this URL:|
Gutch M, Sahani KK, Bhattacharjee A, Kumar S, Shakya S. Wolfram syndrome: A rare mimic of type 1 diabetes mellitus. CHRISMED J Health Res [serial online] 2016 [cited 2020 Jul 4];3:229-31. Available from: http://www.cjhr.org/text.asp?2016/3/3/229/183753
| Introduction|| |
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. One of the rare forms of diabetes is Wolfram syndrome, which is an inherited or sporadic neurodegenerative disorder, presenting as insulin-dependent Diabetes insipidus, insulin-dependent diabetes mellitus, optic atrophy, and deafness (DIDMOAD). However, there are less well-known manifestations of this syndrome, which includes neuropsychiatric manifestations, reproductive abnormalities, limited joint mobility, and cardiovascular and gastrointestinal autonomic neuropathy, any of which can be the presenting feature. 
| Case report|| |
A 14-year-old boy presented to the emergency unit in altered sensorium. There was no history of fever, headache, convulsions, trauma, or any other contributing factors. Neither did we record a history of polyuria, visual deficit nor hearing loss. Investigations revealed high blood glucose levels (430 mg/dl), metabolic acidosis (pH = 7.05, HCO3 = 12 meq/l), and urine was positive for the presence of ketones (dipstick = 3+). We tested for glutamic acid decarboxylase-65 antibodies which turned out to be negative. Height: 134 cm, weight: 28 kg, and body mass index: 15.59 kg/m 2 . Tanner scoring was A2 P3 TV 8 mL bilaterally. He has been well with no chronic medical problems, no hospitalizations, and no surgeries. The child is a product of nonconsanguineous marriage and uneventful 9 months vaginal delivery in the hospital. There were no history of feeding difficulties, seizures, neonatal jaundice, and lactose intolerance and developmental milestones - gross motor, fine motor, social delay. The child is average in studies at school. Social, family, and peer interactions are normal and no behavioral problems. He was treated according to standard protocols for diabetic ketoacidosis.
Renal, hepatic, and thyroid functions and other blood test were normal. Urea: 30 mg/dL, creatinine: 1 mg/dL, creatinine clearance = 85 mL/min, calcium: 10.5 mg/dL, phosphorus: 3.6 mg/dL, sodium: 142 mg/dL, potassium: 4.9 mg/dL, hemoglobin A1c: 13.3%, alanine transaminase: 32 IU/L, aspartate transaminase: 35 IU/L, alkaline phosphatase: 218 U/L, total bilirubin: 1.0 mg/dL, direct bilirubin: 0.3 mg/dL, T4: 9.2 ng/dL, T3: 137 ng/dL, thyroid-stimulating hormone: 2.9 mU/L, follicle stimulating hormone (basal): 2.3 mIU/mL (n = 1-10 mIU/mL), luteinizing hormone (basal): 4.6 mIU/mL (n = 2-8 mIU/mL), prolactin: 3.46 ng/dL (n = 2-15 ng/dL), fasting morning cortisol: 9.5 μg/dl (n = 5-25 μg/dL), testosterone: 15.36 nmol/L (n = 10-35 nmol/L), and X-ray hand (T2-weighted): 12.8 years (bone age). Magnetic resonance imaging of the brain was diffuse cerebral degeneration along with absent posterior pituitary bright spot.
On recovering consciousness, patient complained of decreased vision in both eyes. He never had any issues with his vision in the past. An ophthalmology consultation was taken. On funduscopic examination, bilateral optic atrophy was recognized, and there was no evidence of diabetic retinopathy [Figure 1]. After adequate blood sugar control and titration of insulin doses, he was discharged. The presence of any renal tract anomalies was ruled out with the help of an abdominal ultrasonogram. An apical four chamber view shows drop out of size 2.8 mm in atrial septum with dilatation right atrium and right ventricle suggestive of atrial septal defect [Figure 2].
|Figure 1: Photographic image of the patient right and left eye showing optic atrophy without diabetic retinopathy|
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|Figure 2: An apical four chamber view shows drop out of size 2.8 mm (White arrow) in atrial septum with dilatation right atrium and right ventricle|
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On careful inquisition, we discovered that he had two siblings, both sisters, who was diagnosed with insulin-dependent diabetes mellitus (IDDM) and had attempted to commit suicide. These attempts were reportedly unprovoked as there was no evidence of mental retardation in our patient or his family members. He belonged to a middle-class family, and his performance in school was average.
On follow-up, he complained of being hard of hearing and increased frequency and quantity of micturition (both daytime and nocturnal). We took consultation from the Ear, Nose, and Throat Department, and he was diagnosed to have sensorineural hearing loss as was evident from audiometry findings. The 24 h urine output, urine osmolality, serum osmolality, urine sodium levels, and formal water deprivation test along with absent posterior pituitary bright spot were suggestive of diabetes insipidus [Table 1].
| Discussion|| |
Wolfram syndrome is an autosomal recessive neurodegenerative disorder characterized by the presence of IDDM, blindness from optic atrophy, hearing loss, and other neurological features. It occurs due to loss of function mutations of the Wolfram syndrome 1 (WFS1) gene  which encodes the protein wolframin. The initial features of this syndrome are IDDM and optic atrophy which invariably occur in the first decade of life  while sensorineural deafness and diabetes insipidus manifests in the second decade, followed by other neurological and renal tract abnormalities and renal later in life.  The most common cause of death in these patients is central respiratory failure due to brainstem involvement. 
Wolfram syndrome is also associated with an increased risk of psychiatric disorders, particularly depression and suicidal tendencies, which is found in higher frequencies in subjects with 611R/611R genotype of WFS1 mutation.  Besides this, Wolfram syndrome has also been linked to sleep and cognitive and other psychiatric abnormalities. 
Ophthalmological findings in Wolfram syndrome include optic atrophy, constriction of visual fields, and impaired visual acuity and color vision.  However, diabetic retinopathy is seen very rarely.  As regards, urinary tract abnormalities, upper urinary tract dilatation, bladder dysfunction, and atonia are the common presentations.  The average life expectancy of patients affected with Wolfram syndrome is about 30 years; common causes of death include renal failure secondary to recurrent infections and central respiratory failure.
There are very few case reports of this rare syndrome from India. Besides the classical signs and symptoms, additional features such as neuropsychiatric symptoms, central hypogonadism, and vitreous hemorrhage were described by Saran et al.  in their case series. In another case series reported by Ganie et al.,  optic atrophy was present in all the affected children while sensorineural hearing loss and central diabetes insipidus were present in four out of seven patients. Viswanathan et al.  described an affected child who had developed DM, central diabetes insipidus, optic atrophy, sensorineural hearing loss along with diabetic cystopathy, and depression. The association of atrial septal defect, severe pulmonary stenosis, and hypoplastic right ventricle with Wolfram syndrome was for the 1 st time reported by Mir et al. 
Our patient presented with IDDM, optic atrophy, and sensorineural hearing loss in the second decade of life. We did not perform a genetic analysis; however, there was a history of IDDM and suicidal tendencies among his two sisters. Such patients should be regularly followed to detect other expected anomalies and be treated for any treatable conditions.
| Conclusion|| |
Wolfram syndrome manifests as a combination of young onset nonimmune IDDM and progressive optic atrophy in all patients with added diabetes insipidus and sensory neural deafness in 70% of the patients; hence, it referred to as DIDMOAD syndrome.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]