Wolfram Syndrome-2, a Cause of Severe Gastrointestinal Bleeding: A Case Series and a Literature Review.

Background: There are very few reports of Wolfram syndrome-2 (WFS2) in the literature, and understanding of involvement of the gastrointestinal (GI) tract in the syndrome is limited. Objectives: This study aims to describe the clinical presentations of a large number of WFS2 patients with specific focus on their GI manifestations. Methods: This is a retrospective case series study. Patients who were homozygous for the CISD2 gene mutation were identified through the genetic department of Al-Makassed hospital. Their medical records were reviewed, and biometric data have been obtained. The data were collected and arranged on a data sheet, and descriptive analysis was done using SPSS. Results: Thirteen patients from 9 families were identified; diabetes mellitus was present in 6 of them, optic atrophy in 5, diabetes insipidus (DI) in 5, and deafness in 2. All of the patients had GI manifestations with abnormal findings on upper endoscopy. Dysmorphic facial features and abnormal findings on brain MRI were present in 3 of our patients. The GI manifestations including GI bleeding and severe ulcerations were the first to appear in 9 of them, while anemia in the remaining 4. Conclusion: This is the largest study to date describing patients with WFS2. This study's evidence shows the prominent presence of GI involvement, and the severe findings on endoscopy, including duodenal, gastric, and esophageal ulcerations and strictures. Unlike in the Jordanian report, some of the patients in our report also have DI.

Case Report: Ophthalmologic Evaluation Over a Long Follow-Up Time in a Patient With Wolfram Syndrome Type 2: Slowly Progressive Optic Neuropathy as a Possible Clinical Finding.

Wolfram syndrome (WFS) is a rare autosomal recessive neurodegenerative disease whose diagnosis requires diabetes mellitus and optic atrophy (OA). WFS includes a wide spectrum of other possible complications such as diabetes insipidus, sensorineural deafness, urinary tract problems, neurological and psychiatric disorders. Most WFS patients show type 1 syndrome (WFS1) caused by mutations in the WFS1 gene, encoding Wolframin protein, while few patients are affected by WFS type 2 (WFS2) due to a pathogenetic variants in the CISD2 gene encoding an endoplasmic reticulum intermembrane small protein. WFS2 is considered a phenotypic and genotypic variant of WFS, from which differs only for the increased risk of bleeding and presence of peptic ulcers. OA and diabetes are considered cardinal features of WFS. We hereby report the ophthalmologic evaluation in a patient, previously described, with WFS2 after 8 years of follow-up. A 20-year-old white woman was referred to our retinal center for the first time in 2012 following a diagnosis of a novel intragenic exon 2 CISD2 homozygous deletion, for the suspicion of an associated bilateral OA. Fundus examination, spectral-domain optical coherence tomography, visual field, visual evoked potentials were performed and confirmed the presence of an optic neuropathy that remained stable over 8 years follow up. A slowly progressive optic neuropathy, rather than OA can characterize patients with WFS2 and CISD2 intragenic deletion.