title: False diagnosis of type 1 diabetes mellitus and its complications in Wolfram syndrome--is it the reason for the low number of reported cases of this abnormality?
abstract: Wolfram syndrome (WS), also known as DIDMOAD (Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy and Deafness), is a rare autosomal recessive syndrome (1/770,000 in the United Kingdom), characterised by juvenile onset of diabetes mellitus, optic nerve atrophy, diabetes insipidus, sensorineural deafness, renal tract and neurological abnormalities, and primary gonadal atrophy. WS is caused mainly by biallelic mutations in the WFS1 gene, which encodes wolframin. Wide tissue distribution of wolframin and many mutations in the wolframin gene resulting in Wolfram syndrome may contribute to different phenotypes and the unusual combinations of clinical features. We describe a female patient with Wolfram syndrome diagnosed at the age of 25, with a previous false diagnosis of type 1 diabetes mellitus and misdiagnosed diabetic complications. The patient was found to be a compound heterozygote for two novel mutations in exon 8 of WFS1 gene: a 2-bp deletion AT at nt 1539 leading to a frameshift (Y513fs) and a single-base substitution 1174C > T resulting in a stop codon (Q392X). A detailed analysis of the patient's medical history and a review of the literature suggest that many cases of Wolfram syndrome may remain undiagnosed due to misdiagnosis as type 1 diabetes mellitus and incorrect interpretation of clinical symptoms of neurodegenerative abnormalities, especially in their early stages.
authors.affiliation: Department of Diabetology and Internal Diseases, Pomeranian Medical University Szczecin, Poland. kasho@interia.pl
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Homa
authors.affiliation: Department of Diabetology and Internal Diseases, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Adam
authors.initials: A
authors.lastname: Stefański
authors.affiliation: Department of Pediatrics, Oncology, Hematology and Diabetology, Medical University, Łódź, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Zmysłowska
authors.affiliation: Department of Diabetology and Internal Diseases, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Molęda
authors.affiliation: Department of Diabetology and Internal Diseases, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Marta Ewa
authors.initials: ME
authors.lastname: Bryśkiewicz
authors.affiliation: Department of Diabetology and Internal Diseases, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Liliana
authors.initials: L
authors.lastname: Majkowska
mesh_terms: D000328:Adult; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000175:diagnosis / Q000378:metabolism; D005189:False Positive Reactions; D005260:Female; D017127:Glycation End Products, Advanced; D006801:Humans; D012709:Serum Albumin / Q000378:metabolism; D014929:Wolfram Syndrome / Q000175:diagnosis* / Q000209:etiology* / Q000378:metabolism; D000093423:Glycated Serum Albumin
chemical_list: D017127:Glycation End Products, Advanced; D012709:Serum Albumin; D000093423:Glycated Serum Albumin