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Mitochondrial Function in Schimke-Immunoosseous Dysplasia

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Abstract

Schimke-immunoosseous dysplasia (SIOD) is a multisystemic disorder caused by a mutation of a putative chromatin remodelling protein. Spondyloepiphyseal dysplasia with disproportionate growth deficiency, nephrotic syndrome with focal and segmental glomerulosclerosis, defective cellular immunity, and transient ischemic attacks are major clinical features in the severe form of SIOD. In the present study we tested the hypothesis that mitochondrial dysfunction may be an underlying pathophysiologic mechanism in this multisystemic disease. Mitochondrial parameters were studied in blood (lactate, pyruvate, ketone bodies, alanine) and in urine (organic acids) of four patients with the severe form of SIOD. Activities of respiratory chain enzymes were measured spectrophotometrically in fibroblasts of two of these patients. In patients with the severe form of SIOD normal concentrations of lactate as well as normal lactate/pyruvate- and ketone-body ratios were found in plasma. Alanine, the long-term parameter for lactate, was normal as well; metabolites of the citrate cycle were not found in the urine. Activities of respiratory chain enzymes I–V were not significantly reduced in fibroblasts from two patients with the severe form of SIOD. There was no evidence for mitochondrial dysfunction in SIOD. The underlying pathophysiology of SIOD remains unclear.

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Abbreviations

SIOD:

Schimke-immunoosseous dysplasia

TIA:

transient ischemic attack

SMARCAL 1:

SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1

NO:

nitric oxide

NOS:

nitric oxide synthetase

References

  • Bensadoun, A., and Weinstein, D. (1976). Assay of proteins in the presence of interfering material. Anal. Biochem. 70:241–250.

    Article  PubMed  Google Scholar 

  • Boerkoel, C.F., Nowaczyk, M.J.M., Blaser, S.I., Meschino, W.S., and Weksberg, R. (1998). Schimke immunoosseous dysplasia complicated by moyamoya phenomenon. Am. J. Med. Genet. 78:118–122.

    Article  PubMed  Google Scholar 

  • Boerkoel, C.F., O’Neill, S., Andre, J.L., Benke, P.J., Bogdanovic, R., Bulla, M., Burguet, A., Cockfield, S., Cordeiro, I., Ehrich, J.H., Frund, 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., Milford, D.V., Ormala, T., Rener-Primec, Z., and Weksberg, R. (2000). Manifestations and treatment of Schimke immunoosseous dysplasia: Fourteen new cases and a review of the literature. Eur. J. Pediatr. 159:1–7.

    Article  PubMed  Google Scholar 

  • Boerkoel, C.F., Takashima, H., John, J., Yan, J., Stankiewicz, P., Rosenbarker, L., Andre, J.L., Bogdanovic, R., Burguet, A., Cockfield, S., Cordeiro, I., Frund, S., Illies, F., Joseph, M., Kaitila, I., Lama, G., Loirat, C., McLeod, D.R., Milford, D.V., Petty, E.M., Rodrigo, F., Saraiva, J.M., Schmidt, B., Smith, G.C., Spranger, J., Stein, A., Thiele, H., Tizard, J., Weksberg, R., Lupski, J.R., and Stockton, D.W. (2002). Mutant chromatin remodeling protein SMARCAL1 causes Schimke immunoosseous dysplasia. Nat. Genet. 30(2):215–220.

    Article  PubMed  Google Scholar 

  • Clark, J.F., Kemp, G.J., and Radda, G.K. (1995). The creatine kinase equilibrium, free [ADP] and myosin ATPase in vascular smooth muscle. J. Theor. Biol. 173:207–211.

    Article  PubMed  Google Scholar 

  • Das, A.M. (1998). Regulation of mitochondrial ATP-synthase activity in human myocardium. Clin. Sci. 94:499–504.

    PubMed  Google Scholar 

  • Das, A.M., Byrd, D.J., and Brodehl, J. (1994). Regulation of the mitochondrial ATP-synthase in human fibroblasts. Clin. Chim. Acta 231:61–68.

    Article  PubMed  Google Scholar 

  • Ehrich, J.H.H., Burchert, W., Schirg, E., Krull, F., Offner, G., Hoyer, P.F., and Brodehl, J. (1995). Steroid-resistant nephrotic syndrome associated with spondyloepiphyseal dysplasia, transient ischemic attacks, and lymphopenia. Clin. Nephrol. 43:89–95.

    PubMed  Google Scholar 

  • Ehrich, J.H.H., Offner, G., Schirg, E., Hoyer, P.F., Helmchen, U., and Brodehl, J. (1990). Association of spondylo-epiphyseal dysplasia with nephrotic syndrome. Pediatr. Nephrol. 4:117–121.

    Article  PubMed  Google Scholar 

  • Kaitilia, I., Savilahti, E., and Ormala, T. (1998). Autoimmune enteropathy in Schimke immunoosseous dysplasia. Am. J. Med. Genet. 77:427–430.

    Article  PubMed  Google Scholar 

  • Kim, P., Jones, J.D., and Sundt, T.M. (1992). High-energy phosphate levels in the cerebral artery during chronic vasospasm after arachnoidal hemorrhage. Neurosurgery 76:991–996.

    Google Scholar 

  • Lou, S., Lamfers, P., McGuire, N., and Boerkoel, C.F. (2002). Longevity in Schimke immunoosseous dysplasia. J. Med. Genet. 39(12):922–925.

    Article  PubMed  Google Scholar 

  • Lücke, T., Christen, H.J., Kanzelmeyer, N., Kohlschütter, A., Ehrich, J.H.H., and Das, A.M. (2003). Remarks on the neurology of immunoosseous dysplasia, Schimke-type (IODS). Nervenheilkd. 22:369–372.

    Google Scholar 

  • Lücke, T., Kemper, M., Neumaier-Probst, E., Bentele, K.H.P., Spranger, J., and Kohlschütter, A. (1999). Das Moya-Moya-Phänomen bei der Immuno-Ossären Dysplasie Schimke. Monatsschr. Kinderheilkd. 147:904, P45.

    Google Scholar 

  • Lücke, T., Marwedel, K.M., Kanzelmeyer, N., Hori, A., Offner, G., Kreipe, H.H., Ehrich, J.H.H., and Das, A.M. (2004). Generalized atherosclerosis sparing the transplanted kidney in Schimke disease. Pediatr. Nephrol. 19(6):672–675.

    Article  PubMed  Google Scholar 

  • Ludman, M.D., Cole, D.E.C., Crocker, J.F.S., and Cohen, M.M. (1993). Schimke immunoosseous dysplasia: Case report and review. Am. J. Med. Genet. 47:793–796.

    Article  PubMed  Google Scholar 

  • Munnich, A., Rötig, A., Chretien, D., Cormier, V., Bourgeron, T., Bonnefont, J.P., Saudubray, J.M., and Rustin, P. (1996a). Clinical presentation in mitochondrial disorders in childhood. J. Inherit. Metab. Dis. 19:521–527.

    Article  Google Scholar 

  • Munnich, A., Rötig, A., Chretien, D., Saudubray, J.M., Cormier, V., and Rustin, P. (1996b). Clinical presentation and laboratory investigations in respiratory chain deficiency. Eur. J. Pediatr. 155:262–274.

    Google Scholar 

  • Nissenkorn, A., Zeharia, A., Lev, D., Fatal-Valevski, A., Barash, V., Gutman, A., Harel, S., and Lerman-Sagie, T. (1999). Multiple presentation of mitochondrial disorders. Arch. Dis. Child 81:209–215.

    PubMed  Google Scholar 

  • Petty, E.M., Yanik, G.A., Hutchinson, R.J., Alter, B.P., Schmalstieg, F.C., Levine, J.E., Ginsburg, D., Robillard, J.E., and Castle, V.P. (2000). Successful bone marrow transplantation in a patient with Schimke immunoosseous dysplasia. J. Pediatr. 137:882–886.

    Article  PubMed  Google Scholar 

  • Schmidt, B., Christen, H.J., Herkenrath, P., Benz-Bohm, G., Muller-Berghaus, J., and Querfeld, U. (1997). Cerebral complications in Schimke immunoosseous dysplasia. Eur. J. Pediatr. 156:789–791.

    Article  PubMed  Google Scholar 

  • Spranger, J., Hinkel, G.K., Stoss, H., Thoenes, W., Wargowski, D., and Zepp, F. (1991). Schimke immunoosseous dysplasia: A newly recognized multisystem disease. J. Pediatr. 119:64–72.

    PubMed  Google Scholar 

  • Tulinius, M.H., Holme, E., Kristiansson, B., Larsson, N.G., and Oldfors, A. (1991). Mitochondrial encephalomyopathies in childhood. II. Clinical manifestations and syndromes. J. Pediatr. 119:251–259.

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pediatrics, Hannover Medical School, Hannover, Germany

    Thomas Lücke, Jochen H. H. Ehrich & Anibh M. Das

  2. Department of Pediatrics, Hannover Medical School, Carl-Neuberg Street 1, D-30623, Hannover, Germany

    Thomas Lücke

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  1. Thomas Lücke
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  2. Jochen H. H. Ehrich
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  3. Anibh M. Das
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Correspondence to Thomas Lücke.

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Lücke, T., Ehrich, J.H.H. & Das, A.M. Mitochondrial Function in Schimke-Immunoosseous Dysplasia. Metab Brain Dis 20, 237–242 (2005). https://doi.org/10.1007/s11011-005-7211-7

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  • DOI: https://doi.org/10.1007/s11011-005-7211-7

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