Wolfram Syndrome Type 2: A Systematic Review of a Not Easily Identifiable Clinical Spectrum

Abstract

Background: Wolfram syndrome (WS) is a rare autosomal recessive disorder that is characterized by the presence of diabetes mellitus, optic atrophy and hearing loss, all of which are crucial elements for the diagnosis. WS is variably associated with diabetes insipidus, neurological disorders, urinary tract anomalies, endocrine dysfunctions and many other systemic manifestations. Since Wolfram and Wagener first described WS in 1938, new phenotypic/genotypic variants of the syndrome have been observed and the clinical picture has been significantly enriched. To date, two main subtypes of WS that associated with two different mutations are known: WS type 1 (WS1), caused by the mutation of the wolframine gene (WS1; 606201), and WS type 2 (WS2), caused by the mutation of the CISD2 gene (WS2; 604928). Methods: A systematic review of the literature was describe the phenotypic characteristics of WS2 in order to highlight the key elements that differentiate it from the classic form. Conclusion: WS2 is the rarest and most recently identified subtype of WS; its clinical picture is partially overlapping with that of WS1, from which it traditionally differs by the absence of diabetes insipidus and the presence of greater bleeding tendency and peptic ulcers.

Wolfram Syndrome: A Curious Case of Repetitive Loss of Consciousness

“…WS, sometimes referred to as DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness) due to its main clinical features as an autosomal-recessive genetic disorder, was first described in 1938 by Wolfram and Wagener [ 1 , 4 ]. They described four siblings born from consanguineous parents who were diagnosed with DM and optic atrophy [ 3 , 8 ]. The main clinical features of WS include DM, central diabetes insipidus, optic nerve atrophy, sensorineural deafness, and other neurologic disabilities and urinary tract problems [ 2 , 3 , 5 ].…”

“…WS type 2, a rare and neurodegenerative type of WS, is caused by mutations in the CDGSH iron-sulfur domain-containing protein 2 ( CIDS2 ) gene [ 1 , 5 ]. CISD2 encodes the protein named small intermembrane endoplasmic reticulum protein, which has a central role in the exchanges between endoplasmic reticulum and mitochondria, in the regulation of mitochondrial homeostasis, and in the activation of apoptosis and autophagy [ 1 , 8 ]. This protein is highly expressed in brain and pancreas tissues [ 1 ].…”

Intelligent Systems for Muscle Tracking: A Review on Sensor‐Algorithm Synergy

“…Symptoms of wolfram syndrome include myoclonic tremor, cerebellar ataxia, and dysarthria. [ 34 ] Wolfram syndrome occurs due to mutations that cause pancreatic beta‐cells to undergo apoptosis. In addition, wolfram syndrome causes demyelination as well as degradation of the nervous system.…”

Hypoglycemic Activity of Plant-Derived Traditional Preparations Associated with Surinamese from African, Hindustani, Javanese, and Chinese Origin: Potential Efficacy in the Management of Diabetes Mellitus

“…An estimated 1-5% of cases of diabetes are caused by conditions other than those mentioned above, including those with a genetic background and those that are non-genetically related. Types of diabetes with a genetic background are neonatal diabetes [14] and maturity-onset diabetes in the young [15], Wolfram syndromerelated (type 1) diabetes [16], and cystic fibrosis-related (type 1) diabetes [17]. Types of diabetes with a non-genetic background are, among others, chronic pancreatitisassociated diabetes, which is usually caused by extensive damage to the exocrine tissue of the pancreas [18], brittle diabetes, which primarily affects patients with type 1 diabetes and manifests as frequent and severe fluctuations in blood glucose levels [19], and Cushing's syndrome-related diabetes [20].…”