ESPE Abstracts

Background: Wolfram syndrome is an autosomal recessive disorder accompanied by diabetes insipidus, diabetes mellitus, optic atrophy and deafness. Mutations in the WFS1 gene are determined in 90% of cases. We present the clinical features of three cases of Wolfram syndrome.

Objective and hypotheses: Case 1: A 14-year-old girl presented with loss of vision. At the age of 3 years she had been diagnosed with type 1 diabetes mellitus with a blood glucose level of 410 mg/dl and ketone positivity in urine at a center to which she presented with symptoms of excessive water consumption and urination. At the age of 8 the water deprivation test was performed, due to symptoms of polyuria and polydipsia and low urinary specific gravity, although her blood glucose levels were normal. She was started on nasal desmopressin therapy with a diagnosis of central diabetes insipidus. Blurred vision had begun at the age of 8, and cataract was determined in the right eye. Optic atrophy was determined at fundus examination following cataract surgery. No consanguinity was identified between the parents, although they came from a very small village. A brother had died from diabetic ketoacidosis at the age of 4 years, while a 24-year-old sister had been diagnosed with type 1 diabetes mellitus. Weight was 38 kg (−2,3 S.D.), height 145 cm (−2,3 S.D.), puberty Tanner stage 3 and blood pressure 110/60. Arthropathy was determined in the fingers. Other system examinations were normal. No loss of hearing was determined at audiometry. Homozygous p.I845N (c 2534T>A) mutation in the WFS1 gene was determined at molecular genetic analysis. The parents were also heterozygous for the same mutation. HbA1c was between 8% and 9% with multiple insulin therapy and exchange list nutrition. Case 2: A 7-year-old male patient presented with polyuria and polydipsia. Vision was reported to be poor since babyhood. Birth weight was 3700 gr, and the parents were second-degree cousins. Weight 35 kg (3.3 S.D.), height 115 cm (−1.2 S.D.), BMI 26.4 kg/m² (3.2 S.D.) and blood pressure 100/60 mmHg. Central type obesity and constant nystagmus were determined. Vision was at the light perception level. Bilateral optic atrophy and pigmented retinopathy were observed at fundus examination. Blood glucose 209 mg/dl. Ketone positive in urine. HbA1c was 7%, and 60 dB sensorial loss was determined at audiometry. No mutation was detected at WFS1 gene analysis.HbA1c was between 7.5% and 8.5% with multiple insulin therapy and exchange list nutrition. Case 3: A 9-year-old girl presented due to polyuria and polydipsia. Loss of vision was reported to have begun after the age of 3 years. Weight 26.5 kg (−0.8 S.D.), height 126.5 cm (−0.5 S.D.), BMY 16.5 kg/m² (0.1 S.D.), puberty stage 1 and absence of vision and light perception were determined. At fundus examination the central area was normal, while abundant salt and pepper pigmentation was observed in the periphery. Other system examinations were normal. The water deprivation test was compatible with central diabetes insipidus. The oral glucose tolerance test was normal. HbA1c was 4.8%. Total block of transmission (complete blindness) was determined with VEP and ERG. No hearing loss was determined at audiometry. The patient was started on desmopressin nasal spray with a diagnosis of central diabetes insipidus and placed under monitoring. Genetic analysis could not be performed.

Conclusion: Clinical features may differ in presentations of Wolfram syndrome. The syndrome may emerge during monitoring even if not all the features are present concurrently at presentation.