P-238: Case report of Wolfram syndrome (ws) in childhood, a challenging diagnosis
G Adami, A Vervloet da Luz, J G Rico, R Biasi, A Riquetto, L Cudízio, L E CalliariAbstract
Introduction
WS is a rare monogenic neurodegenerative disorder with an estimated prevalence of 1:500,000. In its classic form, it is characterized by the association of diabetes mellitus, diabetes insipidus, optic atrophy, and sensorineural hearing loss (DIDMOAD). Diabetes is insulin-dependent, with early onset and absence of autoimmunity. It is frequently treated as Type 1 diabetes until more specific symptoms appear. The syndrome is caused by biallelic variants in the WFS1 gene, which encodes the protein wolframin, leading to cellular stress and death of neurons and pancreatic beta cells.
Objectives
To highlight the importance of considering WS in the differential diagnosis of Type 1 Diabetes, while also emphasizing the challenges associated with investigating the syndrome.
Methods
A 13-year-old female, followed in our outpatient clinic since she was 10, was diagnosed with T1D at 4 years of age, with typical symptoms and glycemia of 755 mg/dL, without DKA. Throughout childhood, she always presented high BG levels, failure to thrive, polyuria, and nocturia. At 13 years of age, she had significant short stature (Z −4.32), Tanner stage M1P1, and social and learning disabilities. Excessive diuresis (more than 5 liters/day) not related to glycemia was noted. She had no visual or auditive complains.
Results
Genetic testing identified two heterozygous variants in the WFS1 gene (p.Ser411Cysfs*131) and (p.Asn714_Ans721dup). Complementary exams were performed: ophthalmologic evaluation revealing early optic atrophy, and audiometry demonstrating bilateral sensorineural hearing loss. The water deprivation test confirmed the diagnosis of diabetes insipidus. DDAVP was introduced, and excessive polyuria resolved.
Conclusions
As diabetes is the first manifestation of most WS patients, many cases are initially treated as type 1 diabetes, which can delay the diagnosis of the syndrome. Access to molecular testing enables earlier diagnosis and improves clinical management.