Background Wolfram syndrome (WS) is a rare genetic disorder causing multiple organ dysfunction. The classical WS features are childhood-onset diabetes mellitus, optic atrophy, deafness, diabetes insipidus, neurological signs, and other abnormalities. Two genes are responsible for clinical features (WFS1 and WFS2). The disease is inherited as an autosomal recessive, but autosomal dominant mutations are also described as WS-related disorders. Clinical presentation is heterogeneous and sometimes misleading. In this report we aim to increase awareness about this syndrome by presenting a case series with genetically confirmed Wolfram syndrome who have variable phenotypic presentation.

Case Report(s) Case 1 The child presented initially at age of 4-year with symptomatic hypoglycemia, further investigation include admission for fasting challenge test revealed normal result. A genetic test was sent as the diabetes presentation and progression suggestive of Maturity Onset Diabetes of Youth (MODY). It was reported as A heterozygous variant in the Wolfram Syndrome 1 (WFS1) gene. Mutation in this gene is associated with an autosomal dominant nonclassical WFS1 spectrum.Further recommendation for this case is to screen for associated morbidities (optic atrophy, Diabetes Insipidus, deafness, and neurological assessment). The parents will also be screened. The parents were counseled for the genetic test and further plan was discussed.

Case 2, This case developed diabetes at the age of 5 years. He presented with hyperglycemia, negative ketoacidosis and negative autoimmune antibodies. He has mild squint in his right eye for which under went surgical correction. His visual acuity deteriorated during his early adolescent period at the age of 11 years and progressed to complete right-eye blindness by the age of 13 years. Screening for Wolfram related disorder revealed mild SNHL,Optic atrophy confirmed with Brain-MRI. However diabetes inspidous was ruled out by water deprivation test. and no neurological manifestation. Genetic test was sent to rule out monogenic diabetes -MODY result was negative for maturity onset diabetes. Subsequent genetic test confirmed heterozygous mutation WSF1 identified both parent screening showed carrier of the gene. The patient is currently an 18-year-old transfer to adult diabetic Care,He is following with other multi-specialty teams. The regular long-term follow-up and monitoring for this case will be very challenging.

Case 3, presented at age of 4years with classical symptoms of diabetes and negative antibodies Genetic testing was done and revealed a homozygous variant was identified in the WFS1 gene.

Pathogenic variants in this gene are associated with autosomal recessive Wolfram syndrome 1 mutation for wolfram syndrome. The parents were tested for the targeted WFS1 gene, and the results are still awaited. Screening for Optic atrophy,diabetes insipidus and hearing defect were normal.

Conclusion(s) Wolfram Syndrome (WS) is a rare genetic syndrome with progressive neurological deterioration. Therefore, genetic testing to identify mutations is crucial in the clinical management of the syndrome. The Syndrome require multispecialty follow up .careful clinical monitoring and supportive care can help patients and improve their quality of life.