Wolfram Syndrome Type 2: A Systematic Review of a Not Easily Identifiable Clinical Spectrum
Abstract
:1. Introduction
2. Materials and Methods
3. Results
3.1. Diabetes Mellitus
3.2. Optic Atrophy
3.3. Sensorineural Hearing Loss
3.4. Diabetes Insipidus
3.5. Endocrinological Disorders
3.6. Neurological Disorders
3.7. Psychiatric Disorders
3.8. Urological Disorders
3.9. Gastrointestinal Disorders
3.10. Bleeding Tendency
3.11. Rheumatological Disorders
Lead Author | CISD2 Mutation | Patients Characteristics | Onset Symptoms | DM | DI | OA | SNHL | ND | PD | UD | ED | IB-PU | PAD | Others |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Al-Sheyyab, M., 2001 [30] | Sequencing data not available | 13 (4 M, 9 F) Mean age: 14 years (6–37) | + | + 11/13 | ||||||||||
Danielpur, L., 2016 [31] | Homozygous mutation IVS1 6G C, p. E37Q | 1 F 24 years at diagnosis | + | - | + | + | + Neurogenic bladder | - | + | - | + | - | ||
Mozzillo, E., 2014 [10] | Homozygous mutation Del(4)(q24)(chr4:103.803.602;103806759, 103.806818;103867350)x0 | 1 F 5 years at diagnosis | PU-IB | + | - | + * | + | + Gastroparesis Neurogenic bladder | - | - | + | + | Malrotation Intestinal intussusception | |
Pourreza, 2020 [32] | Homozygous mutation Missense variant c.310T > C (p.S104P) in exon 2 | 1 M 7 years at diagnosis | DM | + | - | + | - | + Focal cortical gliosis Encephalomalacia | + | Meibomian gland dysfunction | ||||
Rondinelli, 2015 [24] | Homozygous mutation (cDNA: NM_001008388.4:c.103 + 1G > A, DNA Level: Chr4(GRCh37):g.103790345G > A) | 2 F siblings <1 year at diagnosis | PU-IB | + | + 1/2 | + | + | + Neurogenic bladder Abnormal nerve conduction study | + Mood disorder | + 1/2 | + Oligo-amenorrhoea | + | - | Lofgren syndrome Spondyloarthritis HLAB27+ Hypogammaglobulinemia Microcytic anemia |
Rouzier, 2017 [11] | Homozygous mutation (c.215A > G; p.Asn72Ser) | 1 M 45 years at diagnosis | DM | + 8 years | - | + 33 years | - | + Severe neurological impairment Cerebellar ataxia Myoclonic tremor Dysarthria Pseudobulbar syndrome | - | + | - | - | - | Kidney cysts |
Zhang, Y., 2019 [23] | Homozygous mutation (c.272_273del) | 1 M 9 years at diagnosis | DM | + 9 years | + 11 years | + 10 years | + 11 years | Abnormal brain MRI Abnormal EEG | - | - | - | - | - | - |
Riachi, M., 2019 [33] | Exon 3 deletion Chr4.del.83007475–113 025 264 | 1 M 19 years at diagnosis | DM | + | - | + | + | Developmental delay Cerebral atrophy | - | - | - | Ventricular defect | ||
Ajlouni, K., 2002 [34] | Not available sequencing data | 14 patients from 3 Jordanian families | DM/OA | + | - | + | + | Ataxia Abnormal nerve conduction study | + Depression | + | Hypogonadism | - | + |
3.12. Treatment
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Rigoli, L.; Bramanti, P.; di Bella, C.; de Luca, F. Genetic and clinical aspects of Wolfram syndrome 1, a severe neurodegenerative disease. Pediatr. Res. 2018, 83, 921–929. [Google Scholar] [CrossRef] [PubMed]
- Lombardo, F.; Salzano, G.; di Bella, C.; Aversa, T.; Pugliatti, F.; Cara, S.; Valenzise, M.; De Luca, F.; Rigoli, L. Phenotypical and genotypical expression of Wolfram syndrome in 12 patients from a Sicilian district where this syndrome might not be so infrequent as generally expected. J. Endocrinol. Investig. 2014, 37, 195–202. [Google Scholar] [CrossRef]
- Lombardo, F.; Chiurazzi, P.; Hörtnagel, K.; Arrigo, T.; Valenzise, M.; Meitinger, T.; Messina, M.F.; Salzano, G.; Barberi, I.; de Luca, F. Clinical picture, evolution and peculiar molecular findings in a very large pedigree with Wolfram syndrome. J. Pediatr. Endocrinol. Metab. 2005, 18, 1391–1397. [Google Scholar] [CrossRef]
- Wolfram, D.J.; Wagener, H.P. Diabetes mellitus and simple optic atrophy among siblings: Report of four cases. Mayo. Clinproc. 1938, 13, 715–718. [Google Scholar]
- Paley, R.G.; Tunbridge, R.E. Primary optic atrophy in diabetes mellitus. Diabetes 1956, 5, 295–296. [Google Scholar]
- Amr, S.; Heisey, C.; Zhang, M.; Xia, X.J.; Shows, K.H.; Ajlouni, K.; Pandya, A.; Satin, L.S.; El-Shanti, H.; Shiang, R. A homozygous mutation in a novel zinc-finger protein, ERIS, is responsible for Wolfram syndrome 2. Am. J. Hum. Genet. 2007, 81, 673–683. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Barrett, T.G.; Bundey, S.E.; Macleod, A.F. Neurodegeneration and diabetes: UK nationwide study of Wolfram (DIDMOAD) syndrome. Lancet 1995, 346, 1458–1463. [Google Scholar] [CrossRef]
- Zalloua, P.A.; Azar, S.T.; Delépine, M.; Makhoul, N.J.; Blanc, H.; Sanyoura, M.; Lavergne, A.; Stankov, K.; Lemainque, A.; Baz, P.; et al. WS1 mutations are frequent monogenic causes of juvenile-onset diabetes mellitus in Lebanon. Hum. Mol. Genet. 2008, 17, 4012–4021. [Google Scholar] [CrossRef]
- Pacaud, D.; Schwandt, A.; de Beaufort, C.; Casteels, K.; Beltrand, J.; Birkebaek, N.H.; Campagnoli, M.; Bratina, N.; Limbert, C.; O’Riordan, S.; et al. A description of clinician reported diagnosis of type 2 diabetes and other non-type 1 diabetes included in a large international multicentered pediatric diabetes registry (SWEET). Pediatr. Diabetes 2016, 17, 24–31. [Google Scholar] [CrossRef] [Green Version]
- Mozzillo, E.; Delvecchio, M.; Carella, M.; Grandone, E.; Palumbo, P.; Salina, A.; Aloi, C.; Buono, P.; Izzo, A.; d’Annunzio, G.; et al. A novel CISD2 intragenic deletion, optic neuropathy and platelet aggregation defect in Wolfram syndrome type 2. BMC Med. Genet. 2014, 15, 88. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rouzier, C.; Moore, D.; Delorme, C.; Lacas-Gervais, S.; Ait-El-Mkadem, S.; Fragaki, K.; Burte, F.; Serre, V.; Bannwarth, S.; Chaussenot, A.; et al. A novel CISD2 mutation associated with a classical Wolfram syndrome phenotype alters Ca2+ homeostasis and ER-mitochondria interactions. Hum. Mol. Genet. 2017, 26, 1599–1611. [Google Scholar] [CrossRef] [PubMed]
- Gardner, B.M.; Walter, P. Unfolded proteins are Ire1-activating ligands that directly induce the unfolded protein response. Science 2011, 333, 1891–1894. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tamir, S.; Zuris, J.A.; Agranat, L.; Lipper, C.H.; Conlan, A.R.; Michaeli, D.; Harir, Y.; Paddock, M.L.; Mittler, R.; Cabantchik, Z.I.; et al. Nutrient-deprivation autophagy factor-1 (NAF-1): Biochemical properties of a novel cellular target for anti-diabetic drugs. PLoS ONE 2013, 8, e61202. [Google Scholar] [CrossRef] [PubMed]
- Shen, Z.Q.; Huang, Y.L.; Teng, Y.C.; Wang, T.W.; Kao, C.H.; Yeh, C.H.; Tsai, T.F. CISD2 maintains cellular homeostasis. Biochim. Biophys. Acta Mol. Cell Res. 2021, 1868, 118954. [Google Scholar] [CrossRef] [PubMed]
- Di Iorio, V.; Mozzillo, E.; Rosanio, F.M.; di Candia, F.; Genesio, R.; Testa, F.; Iovino, C.; Franzese, A.; Simonelli, F. 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. Front. Pediatr. 2021, 9, 661434. [Google Scholar] [CrossRef]
- Acharya, A.; Raza, S.I.; Anwar, M.Z.; Bharadwaj, T.; Liaqat, K.; Khokhar, M.A.S.; Everard, J.L.; Nasir, A.; Nickerson, D.A.; Bamshad, M.J.; et al. Wolfram-like syndrome with bicuspid aortic valve due to a homozygous missense variant in CDK13. J. Hum. Genet. 2021, 66, 1009–1018. [Google Scholar] [CrossRef]
- Mozzillo, E.; Salzano, G.; Barbetti, F.; Maffeis, C.; Lombardo, F.; Franzese, A.; Delvecchio, M.; Marigliano, M. Survey on etiological diagnosis of diabetes in 1244 Italian diabetic children and adolescents: Impact of access to genetic testing. Diabetes Res. Clin. Pract. 2015, 107, e15–e18. [Google Scholar] [CrossRef]
- Delvecchio, M.; Iacoviello, M.; Pantaleo, A.; Resta, N. Clinical Spectrum Associated with Wolfram Syndrome Type 1 and Type 2: A Review on Genotype-Phenotype Correlations. Int. J. Environ. Res. Public Health 2021, 18, 4796. [Google Scholar] [CrossRef] [PubMed]
- Scaramuzza, A.; Cherubini, V.; Tumini, S.; Bonfanti, R.; Buono, P.; Cardella, F.; d’Annunzio, G.; Frongia, A.P.; Lombardo, F.; Monciotti, A.C.M.; et al. Diabetes Study Group of the Italian Society for Pediatric Endocrinology and Diabetology. Recommendations for self-monitoring in pediatric diabetes: A consensus statement by the ISPED. Acta Diabetol. 2014, 51, 173–184. [Google Scholar] [CrossRef]
- Cano, A.; Molines, L.; Valero, R.; Simonin, G.; Parquis-Flucklinger, V.; Vialettes, B.; the French Group of Wolfarm Syndrome. Microvascular diabetes complications in Wolfram syndrome (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness [DIDMOAD]): An age- and duration-matched comparison with common type 1 diabetes. Diabetes Care 2007, 30, 2327–2330. [Google Scholar] [CrossRef] [Green Version]
- Tranebjærg, L.; Barrett, T.; Rendtorff, N.D. WS1 Wolfram Syndrome Spectrum Disorder. In GeneReviews®; University of Washington: Seattle, WA, USA, 1993. [Google Scholar]
- Al-Till, M.; Jarrah, N.S.; Ajlouni, K.M. Ophthalmologic findings in fifteen patients with Wolfram syndrome. Eur. J. Ophthalmol. 2002, 12, 84–88. [Google Scholar] [CrossRef] [PubMed]
- Zhang, Y.; Feng, L.; Kong, X.; Wu, J.; Chen, Y.; Tian, G. Novel mutations and the ophthalmologic characters in Chinese patients with Wolfram Syndrome. Orphanet J. Rare Dis. 2019, 14, 190. [Google Scholar] [CrossRef]
- Rondinelli, M.; Novara, F.; Calcaterra, V.; Zuffardi, O.; Genovese, S. Wolfram syndrome 2: A novel CISD2 mutation identified in Italian siblings. Acta Diabetol. 2015, 52, 175–178. [Google Scholar] [CrossRef]
- Akturk, H.K.; Yasa, S. Previously unreported abnormalities in Wolfram Syndrome Type 2. Pediatr. Endocrinol. Diabetes Metab. 2017, 23, 107–110. [Google Scholar] [CrossRef]
- Ito, S.; Sakakibara, R.; Hattori, T. Wolfram syndrome presenting marked brain MR imaging abnormalities with few neurologic abnormalities. Am. J. Neuroradiol. 2007, 28, 305–306. [Google Scholar]
- Pakdemirli, E.; Karabulut, N.; Bir, L.S.; Sermez, Y. Cranial magnetic resonance imaging of Wolfram (DIDMOAD) syndrome. Australas. Radiol. 2005, 49, 189–191. [Google Scholar] [CrossRef] [PubMed]
- Swift, R.G.; Sadler, D.B.; Swift, M. Psychiatric findings in Wolfram syndrome homozygotes. Lancet 1990, 336, 667–669. [Google Scholar] [CrossRef]
- Wragg, R.; Dias, R.P.; Barrett, T.; McCarthy, L. Bladder dysfunction in Wolfram syndrome is highly prevalent and progresses to megacystis. J. Pediatr. Surg. 2018, 53, 321–325. [Google Scholar] [CrossRef] [Green Version]
- Al-Sheyyab, M.; Jarrah, N.; Younis, E.; Shennak, M.M.; Hadidi, A.; Awidi, A.; El-Shanti, H.; Ajlouni, K. Bleeding tendency in Wolfram syndrome: A newly identified feature with phenotype genotype correlation. Eur. J. Pediatr. 2001, 160, 243–246. [Google Scholar] [CrossRef]
- Danielpur, L.; Sohn, Y.S.; Karmi, O.; Fogel, C.; Zinger, A.; Abu-Libdeh, A.; Israeli, T.; Riahi, Y.; Pappo, O.; Birk, R. GLP-1-RA Corrects Mitochondrial Labile Iron Accumulation and Improves β-Cell Function in Type 2 Wolfram Syndrome. J. Clin. Endocrinol. Metab. 2016, 101, 3592–3599. [Google Scholar] [CrossRef] [PubMed]
- Pourreza, M.R.; Sobhani, M.; Rahimi, A.; Aramideh, M.; Kajbafzadeh, A.M.; Noori-Daloii, M.R.; Tabatabaiefar, M.A. Homozygosity mapping and direct sequencing identify a novel pathogenic variant in the CISD2 gene in an Iranian Wolfram syndrome family. Acta Diabetol. 2020, 57, 81–87. [Google Scholar] [CrossRef]
- Riachi, M.; Yilmaz, S.; Kurnaz, E.; Aycan, Z.; Çetinkaya, S.; Tranebjærg, L.; Rendtorff, N.D.; Bitner-Glindzicz, M.; Bockenhauer, D.; Hussain, K. Functional assessment of variants associated with Wolfram syndrome. Hum. Mol. Genet. 2019, 28, 3815–3824. [Google Scholar] [CrossRef]
- Ajlouni, K.; Jarrah, N.; El-Khateeb, M.; El-Zaheri, M.; El Shanti, H.; Lidral, A. Wolfram syndrome: Identification of a phenotypic and genotypic variant from Jordan. Am. J. Med. Genet. 2002, 115, 61–65. [Google Scholar] [CrossRef] [PubMed]
- Lu, S.; Kanekura, K.; Hara, T.; Mahadevan, J.; Spears, L.D.; Oslowski, C.M.; Martinez, R.; Yamazaki-Inoue, M.; Toyoda, M.; Neilson, A.; et al. A calcium-dependent protease as a potential therapeutic target for Wolfram syndrome. Proc. Natl. Acad. Sci. USA 2014, 111, E5292–E5301. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Abreu, D.; Stone, S.I.; Pearson, T.S.; Bucelli, R.C.; Simpson, A.N.; Hurst, S.; Brown, C.M.; Kries, K.; Onwumere, C.; Gu, H.; et al. A phase Ib/IIa clinical trial of dantrolene sodium in patients with Wolfram syndrome. JCI Insight 2021, 6, e145188. [Google Scholar]
- Batjargal, K.; Tajima, T.; Jimbo, E.F.; Yamagata, T. Effect of 4-phenylbutyrate and valproate on dominant mutations of WS1 gene in Wolfram syndrome. J. Endocrinol. Investig. 2020, 43, 1317–1325. [Google Scholar] [CrossRef]
- Karmi, O.; Sohn, Y.S.; Marjault, H.B.; Israeli, T.; Leibowitz, G.; Ioannidis, K.; Nahmias, Y.; Mittler, R.; Cabantchik, I.Z.; Nechushtai, R. A Combined Drug Treatment That Reduces Mitochondrial Iron and Reactive Oxygen Levels Recovers Insulin Secretion in NAF-1-Deficient Pancreatic Cells. Antioxidants 2021, 10, 1160. [Google Scholar] [CrossRef]
- Kinsley, B.T.; Swift, M.; Dumont, R.H.; Swift, R.G. Morbidity and mortality in the Wolfram syndrome. Diabetes Care 1995, 18, 1566. [Google Scholar] [CrossRef]
- Pappa, A.; Hausler, M.G.; Veigel, A.; Tzamouranis, K.; Pfeifer, M.W.; Schmidt, A.; Bokamp, M.; Haberland, H.; Wagner, S.; Bruckel, J.; et al. Diabetes mellitus in Friedreich Ataxia: A case series of 19 patients from the German-Austrian diabetes mellitus registry. Diabetes Res. Clin. Pract. 2018, 141, 229–236. [Google Scholar] [CrossRef]
- Bumpus, E.; Hershey, T.; Doty, T.; Ranck, S.; Gronski, M.; Urano, F.; Foster, E.R. Understanding activity participation among individuals with Wolfram Syndrome. Br. J. Occup. Ther. 2018, 81, 348–357. [Google Scholar] [CrossRef]
Clinical Features | WS1 | WS2 |
---|---|---|
Diabetes mellitus | Yes | Yes |
Optic atrophy/neuropathy | Yes | Yes |
Sensorineural deafness | Yes | Yes |
Diabetes insipidus | Yes | No (sporadic cases described) |
Other endocrinological abnormalities | Yes | No (sporadic cases described) |
Neurological disorders | Yes | No (sporadic cases described) |
Psychiatric symptoms | Yes | No (mood disorders described) |
Genitourinary problems | Yes | Yes |
Platelet aggregation defects | No | Yes |
GI ulcers | No | Yes |
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Rosanio, F.M.; Di Candia, F.; Occhiati, L.; Fedi, L.; Malvone, F.P.; Foschini, D.F.; Franzese, A.; Mozzillo, E. Wolfram Syndrome Type 2: A Systematic Review of a Not Easily Identifiable Clinical Spectrum. Int. J. Environ. Res. Public Health 2022, 19, 835. https://doi.org/10.3390/ijerph19020835
Rosanio FM, Di Candia F, Occhiati L, Fedi L, Malvone FP, Foschini DF, Franzese A, Mozzillo E. Wolfram Syndrome Type 2: A Systematic Review of a Not Easily Identifiable Clinical Spectrum. International Journal of Environmental Research and Public Health. 2022; 19(2):835. https://doi.org/10.3390/ijerph19020835
Chicago/Turabian StyleRosanio, Francesco Maria, Francesca Di Candia, Luisa Occhiati, Ludovica Fedi, Francesco Paolo Malvone, Davide Fortunato Foschini, Adriana Franzese, and Enza Mozzillo. 2022. "Wolfram Syndrome Type 2: A Systematic Review of a Not Easily Identifiable Clinical Spectrum" International Journal of Environmental Research and Public Health 19, no. 2: 835. https://doi.org/10.3390/ijerph19020835