WOLFRAM SYNDROME: A CLINICAL CASE REPORT

Abstract

Introduction. Wolfram syndrome is a progressive autosomal recessive neurodegenerative disease that combines diabetes mellitus (DM), diabetes insipidus, sensorineural hearing loss, and optic nerve atrophy, and is also characterized by multiple manifestations of neurological symptoms.Aim: to expand medical knowledge, exchange experience between specialists in related medical specialties through detailed coverage of the medical problem regarding Wolfram syndrome, as a rare disease.Materials and methods. Presented according to CARE standards, the clinical case is a case of Wolfram syndrome type 1 associated with a homozygous mutation in the wolframin gene (Wolframin ER transmembrane glycoprotein 1 – WFS1), confirmed by molecular genetic method of exome sequencing in a certified laboratory of the University of Exeter (UK, Exeter).Description of a clinical case with analysis of literary sources. The WFS1 gene encodes a transmembrane protein of the same name, localized in the endoplasmic reticulum. The formation of an aberrant wolframin protein with a dominant-negative effect or gain of function leads to impaired protein folding, insulin signaling, calcium homeostasis, regulation of apoptosis, and the endoplasmic reticulum stress response with multiorgan involvement.Primary diagnoses, interventions, and outcomes. Cellular dysfunction due to loss of WFS1 functional activity in the pancreas is characterized by β-cell death and decreased insulin secretion, which is characterized, according to literature sources, in 98% of cases by the debut of Wolfram syndrome, as in our patient, in the form of non-autoimmune type 1 DM at the age of about 6 years. But, unlike the data of other researchers, in our patient, hypoinsulinemic hyperglycemia was combined with an anomaly of the urinary system without the primary manifestation of damage to the organs of vision and hearing, which led, first of all, to differentiation with type 5 diabetes in young patients with onset in adulthood. Conclusion. The absence of counter insular immunogenesis, ketoacidosis, microvascular complications, reduced daily insulin requirement, multiorgan involvement at the onset of juvenile DM requires the exclusion of monogenic forms of DM and other genetic syndromes that occur with manifestations of DM.