Generic placeholder image

Endocrine, Metabolic & Immune Disorders - Drug Targets


ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Case Report

Different Phenotypes of Schimke Immuno-Osseous Dysplasia (SIOD) in Two Sisters with the Same Mutation in the SMARCAL1 Gene

Author(s): Ana Castellano-Martinez, Silvia Acuñas-Soto, Raquel De la Varga-Martinez, Moises Rodriguez-Gonzalez*, Francisco Mora-Lopez, Marianela Iriarte-Gahete and Virginia Roldan-Cano

Volume 22, Issue 8, 2022

Published on: 10 May, 2022

Page: [888 - 894] Pages: 7

DOI: 10.2174/1871530322666220223154028

Price: $65


Background: Schimke immuno-osseous dysplasia (SIOD) is a very rare autosomal recessive genetic disease caused by mutations in the SMARCAL1 gene. It is characterized by spondyloepiphyseal dysplasia, T-cell immunodeficiency, hypercromic nevi, hypercholestero-lemia, and steroid-resistant nephrotic syndrome with progressive renal failure to end-stage kidney disease.

Case Presentation: We report two cases of SIOD in sisters, diagnosed after the debut of nephrotic syndrome. Both had a personal history of short stature, acetabular hip dysplasia, and hypercholesterolemia. The first case, a 6-year-old girl, presented peripheral refractory edema, severe arterial hypertension, and progressive decrease of the glomerular filtration rate. Steroid-resistance of nephrotic syndrome was confirmed, treated with tacrolimus without response. Renal function worsened over the following 4 months, so haemodialysis was started. Her sister, a 5-year-old girl, had the steroid-resistant nephrotic syndrome and normal blood pressure and renal function under enalapril treatment. In view of the suspicion of SIOD, genetic studies were carried out, revealing the same mutation in homozygosis.

Conclusion: SIOD has a variable expression with multi-systemic involvement with a short life expectancy. Early diagnosis is important, which can encourage the early start of treatment and anticipation of complications that may be life-threatening.

Keywords: Schimke immuno-osseus dysplasia, SMARCAL1, nephrotic syndrome, end-stage kidney disease, cardiovascular risk, children.

Graphical Abstract
Morimoto, M.; Choi, K.; Boerkoel, C.F.; Cho, K.S. Chromatin changes in SMARCAL1 deficiency: A hypothesis for the gene expression alterations of Schimke immuno-osseous dysplasia. Nucleus, 2016, 7(6), 560-571.
[] [PMID: 27813696]
Boerkoel, C.F.; O’Neill, S.; André, J.L.; Benke, P.J.; Bogdanovíć, R.; Bulla, M.; Burguet, A.; Cockfield, S.; Cordeiro, I.; Ehrich, J.H.; Fründ, S.; Geary, D.F.; Ieshima, A.; Illies, F.; Joseph, M.W.; Kaitila, I.; Lama, G.; Leheup, B.; Ludman, M.D.; McLeod, D.R.; Medeira, A.; Mil-ford, D.V.; Ormälä, T.; Rener-Primec, Z.; Santava, A.; Santos, H.G.; Schmidt, B.; Smith, G.C.; Spranger, J.; Zupancic, N.; Weksberg, R. Manifestations and treatment of Schimke immuno-osseous dysplasia: 14 new cases and a review of the literature. Eur. J. Pediatr., 2000, 159(1-2), 1-7.
[] [PMID: 10653321]
Santangelo, L.; Gigante, M.; Netti, G.S.; Diella, S.; Puteo, F.; Carbone, V.; Grandaliano, G.; Giordano, M.; Gesualdo, L. A novel SMAR-CAL1 mutation associated with a mild phenotype of Schimke immuno-osseous dysplasia (SIOD). BMC Nephrol., 2014, 15(1), 41.
[] [PMID: 24589093]
Schimke, R.N.; Horton, W.A.; King, C.R. Chondroitin-6-sulphaturia, defective cellular immunity, and nephrotic syndrome. Lancet, 1971, 2(7733), 1088-1089.
[] [PMID: 4106927]
Pedrosa, A.K.; Torres, L.F.; Silva, A.C.; Dantas, A.B.; Zuntini, K.L.; Aguiar, L.C. Rare case of nephrotic syndrome: Schimke syndrome. J. Bras. Nefrol., 2016, 38(3), 370-373.
[] [PMID: 27737398]
Puccetti, M.V.; Fischer, M.A.; Arrate, M.P.; Boyd, K.L.; Duszynski, R.J.; Bétous, R.; Cortez, D.; Eischen, C.M. Defective replication stress response inhibits lymphomagenesis and impairs lymphocyte reconstitution. Oncogene, 2017, 36(18), 2553-2564.
[] [PMID: 27797382]
Morimoto, M.; Lewis, D.B.; Lücke, T.; Boerkoel, C.F. Schimke Immunoosseous Dysplasia. In: GeneReviews; Adam, M.P.; Ardinger, H.H.; Pagon, R.A.; Wallace, S.E.; Bean, L.J.H.; Gripp, K.W.; Mirzaa, G.M.; Amemiya, A., Eds.; University of Washington: Seattle, 2002; pp. 1993-2022.
Sogkas, G.; Dubrowinskaja, N.; Bergmann, A.K.; Lentes, J.; Ripperger, T.; Fedchenko, M.; Ernst, D.; Jablonka, A.; Geffers, R.; Baumann, U.; Schmidt, R.E.; Atschekzei, F. Progressive immunodeficiency with gradual depletion of B and CD4+ T cells in immunodeficiency, cen-tromeric instability and facial anomalies syndrome 2 (ICF2). Diseases, 2019, 7(2), 34.
[] [PMID: 30987377]
Carroll, C.; Hunley, T.E.; Guo, Y.; Cortez, D. A novel splice site mutation in SMARCAL1 results in aberrant exon definition in a child with Schimke immunoosseous dysplasia. Am. J. Med. Genet. A., 2015, 167A(10), 2260-2264.
[] [PMID: 25943327]
Clewing, J.M.; Antalfy, B.C.; Lücke, T.; Najafian, B.; Marwedel, K.M.; Hori, A.; Powel, R.M.; Do, A.F.; Najera, L.; SantaCruz, K.; Hicks, M.J.; Armstrong, D.L.; Boerkoel, C.F. Schimke immuno-osseous dysplasia: A clinicopathological correlation. J. Med. Genet., 2007, 44(2), 122-130.
[] [PMID: 16840568]
Trautmann, A.; Vivarelli, M.; Samuel, S.; Gipson, D.; Sinha, A.; Schaefer, F.; Hui, N.K.; Boyer, O.; Saleem, M.A.; Feltran, L. Mül] ler-Deile, J.; Becker, J.U.; Cano, F.; Xu, H.; Lim, Y.N.; Smoyer, W.; Anochie, I.; Nakanishi, K.; Hodson, E.; Haffner, D. IPNA clinical] practice recommendations for the diagnosis and management of children with steroid-resistant nephrotic syndrome. Pediatr. Nephrol., 2020, 35(8), 1529-1561.
[] [PMID: 32382828]
Xiong, S.; Shuai, L.; Li, X.; Dang, X.; Wu, X.; He, Q. Podocytic infolding in Schimke immuno-osseous dysplasia with novel SMARCAL1 mutations: A case report. BMC Nephrol., 2020, 21(1), 170.
[] [PMID: 32393263]
Jackson, S.P.; Calkin, A.C. The clot thickens--oxidized lipids and thrombosis. Nat. Med., 2007, 13(9), 1015-1016.
[] [PMID: 17828215]
Morimoto, M.; Yu, Z.; Stenzel, P.; Clewing, J.M.; Najafian, B.; Mayfield, C.; Hendson, G.; Weinkauf, J.G.; Gormley, A.K.; Parham, D.M.; Ponniah, U.; André, J.L.; Asakura, Y.; Basiratnia, M.; Bogdanović, R.; Bokenkamp, A.; Bonneau, D.; Buck, A.; Charrow, J.; Cochat, P.; Cordeiro, I.; Deschenes, G.; Fenkçi, M.S.; Frange, P.; Fründ, S.; Fryssira, H.; Guillen-Navarro, E.; Keller, K.; Kirmani, S.; Kobelka, C.; Lamfers, P.; Levtchenko, E.; Lewis, D.B.; Massella, L.; McLeod, D.R.; Milford, D.V.; Nobili, F.; Saraiva, J.M.; Semerci, C.N.; Shoemaker, L.; Stajić, N.; Stein, A.; Taha, D.; Wand, D.; Zonana, J.; Lücke, T.; Boerkoel, C.F. Reduced elastogenesis: A clue to the arteriosclerosis and emphysematous changes in Schimke immuno-osseous dysplasia? Orphanet J. Rare Dis., 2012, 7(1), 70.
[] [PMID: 22998683]
Lücke, T.; Marwedel, K.M.; Kanzelmeyer, N.K.; Hori, A.; Offner, G.; Kreipe, H.H.; Ehrich, J.H.; Das, A.M. Generalized atherosclerosis sparing the transplanted kidney in Schimke disease. Pediatr. Nephrol., 2004, 19(6), 672-675.
[] [PMID: 15054643]
Hari, P.; Khandelwal, P.; Smoyer, W.E. Dyslipidemia and cardiovascular health in childhood nephrotic syndrome. Pediatr. Nephrol., 2020, 35(9), 1601-1619.
[] [PMID: 31302760]
Beleford, D.T.; Diab, M.; Qubty, W.F.; Malloy, M.J.; Long, R.K.; Shieh, J.T. Schimke immunoosseous dysplasia and management consid-erations for vascular risks. Am. J. Med. Genet. A., 2019, 179(7), 1246-1252.
[] [PMID: 31039288]
Hossein Babaei, A.; Inaloo, S.; Basiratnia, M.; Derakhshan, A. Early onset cerebral infarction in schimke immuno-osseous dysplasia. Iran. J. Child. Neurol., 2018, 12(3), 126-132.
[PMID: 30026777]
Motoyama, O.; Inoue, M.; Hasegawa, A.; Sakai, K.; Kawamura, T.; Aikawa, A.; Iitaka, K. Twenty-four-year-old male patient with infantile onset of Schimke immuno-osseous dysplasia. Pediatr. Int., 2010, 52(3), e128-e130.
[] [PMID: 20723108]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy