Abstract
Schimke-immuno-osseous dysplasia (SIOD) is a multisystem disorder caused by a mutation of the chromatin remodeling protein. The main clinical findings are spondyloepiphyseal dysplasia with dysproportional growth deficiency, nephrotic syndrome with focal and segmental glomerulosclerosis, and defective cellular immunity. Transitory ischemic attacks due to vaso-occlusive processes are still an untreatable and life-limiting complication in patients with SIOD. The underlying pathophysiology of vaso-occlusive processes in SIOD is unclear. We report the clinical and pathological findings of the eldest published patient with the severe form of SIOD, who died at the age of 23 years due to pulmonary hypertension with subsequent right heart failure. The autopsy revealed a severe generalized atherosclerosis including the brain, heart, and pulmonary arteries. However, the kidney that was transplanted at the age of 5 years showed a good graft function without glomerular sclerosis and with only minimal nephrosclerosis on histology. Thus, the absence of severe vaso-occlusive processes in the transplanted organ and in the severely atherosclerotic host may indicate that the vaso-occlusive processes in SIOD are not caused by post-transplant cardiovascular morbidity such as arterial hypertension and hyperlipidemia. Instead, vascular factors of the host such as endothelial dysfunction may explain the pathophysiology of atherosclerosis in SIOD.
References
Boerkoel CF, O’Neill S, Andre JL, Benke PJ, Bogdanovic R, Bulla M, Burguet A, Cockfield S, Cordeiro I, Ehrich JH, Frund S, Geary DF, Ieshima A, Illies F, Joseph MW, Kaitila I, Lama G, Leheup B, Ludman MD, McLeod DR, Medeira A, Milford DV, Ormala T, Rener-Primec Z, Weksberg R (2000) Manifestations and treatment of Schimke immuno-osseous dysplasia: 14 new cases and a review of the literature. Eur J Pediatr 159:1–7
Schimke RN, Horton WA, King CR (1971) Chondroitin-6-sulphate-uria, defective cellular immunity and nephritic syndrome. Lancet II:1088–1089
Schimke RN, Horton WA, King CR, Martin NL (1974) Chondroitin-6-sulphate mucopolysaccaridosis in conjunction with lymphopenia, defective cellular immunity and nephritic syndrome. Birth Defects 10:258–266
Spranger J, Hinkel GK, Stoss H, Thoenes W, Wargowski D, Zepp F (1991) Schimke immuno-osseous dysplasia: a newly recognized multisystem disease. J Pediatr 119:64–72
Ehrich JHH, Offner G, Schirg E, Hoyer PF, Helmchen U, Brodehl J (1990) Association of spondylo-epiphyseal dysplasia with nephrotic syndrome. Pediatr Nephrol 4:117–121
Gilchrist DM, Harley FL (1992) Schimke immuno-osseous dysplasia. J Pediatr 120:497
Hashimoto K, Takeuchi A, Ieshima A, Takada M, Kasagi M (1994) Juvenile variant of Schimke immunoosseous dysplasia. Am J Med Genet 49:266–269
Ehrich JHH, Burchert W, Schirg E, Krull F, Offner G, Hoyer PF, Brodehl J (1995) Steroid resistant nephrotic syndrome associated with spondyloepiphyseal dysplasia, transient ischemic attacks and lymphopenia. Clin Nephrol 43:89–95
Schmidt B, Christen HJ, Herkenrath P, Benz-Bohm G, Muller-Berghaus J, Querfeld U (1997) Cerebral complications in Schimke immuno-osseous dysplasia. Eur J Pediatr 156:789–791
Boerkoel CF, Nowaczyk MJM, Blaser SI, Meschino WS, Weksberg R (1998) Schimke immunoosseous dysplasia complicated by moyamoya phenomenon. Am J Med Genet 78:118–122
Lücke T, Kemper M, Neumaier-Probst E, Bentele KHP, Spranger J, Kohlschütter A (1999) Das Moya-Moya-Phänomen bei der Immuno-Ossären Dysplasie Schimke. Monatsschr Kinderheilkd 147:904
Boerkoel CF, Takashima H, John J, Yan J, Stankiewicz P, Rosenbarker L, Andre JL, Bogdanovic R, Burguet A, Cockfield S, Cordeiro I, Frund S, Illies F, Joseph M, Kaitila I, Lama G, Loirat C, McLeod DR, Milford DV, Petty EM, Rodrigo F, Saraiva JM, Schmidt B, Smith GC, Spranger J, Stein A, Thiele H, Tizard J, Weksberg R, Lupski JR, Stockton DW (2002) Mutant chromatin remodeling protein SMARCAL1 causes Schimke immuno-osseous dysplasia. Nat Genet 30:215–220
Da Fonseca MA (2000) Dental findings in the Schimke immuno-osseous dysplasia. Am J Med Genet 93:158–160
Dhillon AS, Chapman S, Milford DV (2001) Cerebellar defect associated with Schimke immuno-osseous dysplasia. Eur J Pediatr 160:372–374
Rodrigo F, Ferrer-Canabate J, Gracia S, Tovar I, Borraja E, Tellez C, Martinez P (2001) Schimke immunoosseous dysplasia syndrome (SIOD). Pediatr Nephrol 16:606–608
Iseki K, Fukiyama K (1996) Predictors of stroke in patients receiving chronic hemodialysis. Kidney Int 50:1672–1675
Goldstein S, Duhamel G, Laudat MH, Berthelier M, Hervy C, Tete MJ, Broyer M (1984) Plasma lipids, lipoproteins and apolipoproteins AI, AII, and B in renal transplanted children: what risk for accelerated atherosclerosis? Nephron 38:87–92
Kaitilia I, Savilahti E, Ormala T (1998) Autoimmune enteropathy in Schimke immunoosseous dysplasia. Am J Med Genet 77:427–430
Kim P, Jones JD, Sundt TM (1992) High-energy phosphate levels in the cerebral artery during chronic vasospasm after arachnoidal hemorrhage. Neurosurgery 76:991–996
Clark JF, Kemp GJ, Radda GK (1995) The creatine kinase equilibrium, free [ADP] and myosin ATPase in vascular smooth muscle. J Theor Biol 173:207–211
Moncada S, Higgs A (1993) The l-arginine-nitric oxide pathway. N Engl J Med 329:2002–2012
Cooke JP, Dzau VJ (1997) Nitric oxide synthase: role in the genesis of vascular disease. Annu Rev Med 48:489–509
Cayatte AJ, Palacino JJ, Horten K, Cohen RA (1994) Chronic inhibition of nitric oxide production accelerates neointima formation and impairs endothelial function in hypercholesterolemic rabbits. Arterioscler Thromb 14:753–759
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Lücke, T., Marwedel, K.M., Kanzelmeyer, N.K. et al. Generalized atherosclerosis sparing the transplanted kidney in Schimke disease. Pediatr Nephrol 19, 672–675 (2004). https://doi.org/10.1007/s00467-004-1426-z
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00467-004-1426-z