Skeletal Radiology

, Volume 41, Issue 11, pp 1479–1487 | Cite as

Metaphyseal chondromatosis combined with D-2-hydroxyglutaric aciduria in four patients

  • Hye Jung Choo
  • Tae-Joon Cho
  • Junghan Song
  • George E. Tiller
  • Sun Hee Lee
  • Gunbo Park
  • In Sook Lee
  • Ralph Lachman
  • Andrea Superti-Furga
  • Ok-Hwa Kim
Case Report

Abstract

We report four patients who presented with a severe form of metaphyseal chondromatosis in association with D-2-hydroxyglutaric aciduria (D-2-HGA). All patients showed splaying columns of irregular ossification defects with bulbous metaphyses of the long tubular bones, as well as remarkable involvement of the short tubular and flat bones. The vertebral bodies revealed platyspondyly with irregular, stippled endplates. D-2-HGA has been described as a neurometabolic disorder manifesting a broad range of impairment in mental and motor development. Although hydroxyglutaric acid was excreted in high amounts in the urine of all four patients described herein, no significant neurologic abnormalities were evident. This unusual combination of characteristic skeletal and metabolic abnormalities has rarely been reported. Thus, our report will facilitate the recognition of this distinctive entity, and we suggest that a urine organic acid screening be obtained in patients who present with generalized enchondromatosis.

References

  1. 1.
    Talkhani I, Saklatvala J, Dwyer J. D-2-hydroxyglutaric aciduria in association with spondyloenchondromatosis. Skeletal Radiol. 2000;29:289–92.PubMedCrossRefGoogle Scholar
  2. 2.
    Honey E, van Rensburg M, Knoll D, Mienie L, van de Werke I, Beighton P. Spondyloenchondromatosis with D-2-hydroxyglutaric aciduria: a report of a second patient with this unusual combination. Clin Dysmorphol. 2003;12:95–9.PubMedCrossRefGoogle Scholar
  3. 3.
    Bayar A, Acun C, Dursun A, Verhoeven N, Bonafe L, Keser S, et al. Metaphyseal enchondrodysplasia with 2-hydroxy-glutaric aciduria: observation of a third case and further delineation. Clin Dysmorphol. 2005;14:7–11.PubMedCrossRefGoogle Scholar
  4. 4.
    Warman ML, Cormier Daire V, Hall C, Krakow D, Lachman R, LeMerrer M, et al. Nosology and classification of genetic skeletal disorders: 2010 revision. Am J Med Genet A. 2011;155:943–68.CrossRefGoogle Scholar
  5. 5.
    Vissers LELM, Fano V, Martinelli D, Campos-Xavier B, Barbuti D, Cho T-J, et al. Whole-exome sequencing detects somatic mutations of IDH1 in metaphyseal chondromatosis with D-2-hydroxyglutaric aciduria (MC-HGA). Am J Med Genet A. 2011;155:2609–16.CrossRefGoogle Scholar
  6. 6.
    Schorr S, Legum C, Ochshorn M. Spondyloenchondrodysplasia. Radiology. 1976;118:133–9.PubMedGoogle Scholar
  7. 7.
    Spranger J, Kemperdieck H, Bakowski H, Opitz J. Two peculiar types of enchondromatosis. Pediatr Radiol. 1978;7:215–9.PubMedCrossRefGoogle Scholar
  8. 8.
    Menger H, Kruse K, Spranger J. Spondyloenchondrodysplasia. J Med Genet. 1989;26:93–9.PubMedCrossRefGoogle Scholar
  9. 9.
    Uhlmann D, Rupprecht E, Keller E, Hormann D. Spondyloenchondrodysplasia: several phenotypes-the same syndrome. Pediatr Radiol. 1998;28:617–21.PubMedCrossRefGoogle Scholar
  10. 10.
    Tűysűz B, Arapoglu M, Ünger S. Spondyloenchondrodysplasia: clinical variability in three cases. Am J Med Genet. 2004;128A:185–9.PubMedCrossRefGoogle Scholar
  11. 11.
    Renella R, Schaefer E, LeMerrer M, Alanay Y, Kandemir N, Eich G, et al. Spondyloenchondrodysplasia with spasticity, cerebral calcifications, and immune dysregulation: clinical and radiographic delineation of a pleiotropic disorder. Am J Med Genet. 2006;140A:541–50.CrossRefGoogle Scholar
  12. 12.
    Lausch E, Janecke A, Bros M, Trojandt S, Alanay Y, De Laet C, et al. Genetic deficiency of tartrate-resistant acid phosphatase associated with skeletal dysplasia, cerebral calcifications and autoimmunicty. Nat Genet. 2011;43:132–7.PubMedCrossRefGoogle Scholar
  13. 13.
    Van der Knaap M, Jakobs C, Hoffmann G, Duran M, Muntau A, Schweitzer S, et al. D-2-hydroxyglutaric aciduria: further clinical delineation. J Inherit Metab Dis. 1999;22:404–13.PubMedCrossRefGoogle Scholar
  14. 14.
    Craigen WJ, Jakobs C, Sekul EA, Levy ML, Gibson KM, Butler IJ, et al. D-2-hydroxyglutaric aciduria in neonate with seizures and CNS dysfunction. Pediatr Neurol. 1994;10:49–53.15.PubMedCrossRefGoogle Scholar
  15. 15.
    Nyhan WL, Shelton GD, Jakobs C, Homes B, Curry CJ, Vance C, et al. D-2-hydroxyglutaric aciduria. J Child Neurol. 1995;10:137–42.PubMedCrossRefGoogle Scholar
  16. 16.
    Sugita K, Kakinuma H, Okajima Y, Ogawa A, Waanabe H, Niimi H. Clinical and MRI findings in a case of D-2-hydroxyglutaric aciduria. Brain Dev. 1995;17:139–41.PubMedCrossRefGoogle Scholar
  17. 17.
    Struys EA. D-2-hydroxyglutaric aciduria: unraveling the biochemical pathway and the genetic defect. J Inherit Metab Dis. 2006;29:21–9.PubMedCrossRefGoogle Scholar
  18. 18.
    Amary MF, Damato S, Halai D, Eskandarpour M, Berisha F, Bonar F, et al. Ollier disease and Maffucci syndrome are caused by somatic mosaic mutations of IDH1 and IDH2. Nat Genet. 2011;43:1262–5.PubMedCrossRefGoogle Scholar
  19. 19.
    Pansuriya TC, van Eijk R, d'Adamo P, van Ruler MAJH, Kuijjer ML, Oosting J, et al. Somatic mosaic IDH1 and IDH2 mutations are associated with enchondroma and spindle cell hemangioma in Ollier disease and Maffucci syndrome. Nat Genet. 2011;43:1256–61.PubMedCrossRefGoogle Scholar

Copyright information

© ISS 2012

Authors and Affiliations

  • Hye Jung Choo
    • 1
  • Tae-Joon Cho
    • 2
  • Junghan Song
    • 3
  • George E. Tiller
    • 4
  • Sun Hee Lee
    • 5
  • Gunbo Park
    • 6
  • In Sook Lee
    • 7
  • Ralph Lachman
    • 8
  • Andrea Superti-Furga
    • 9
  • Ok-Hwa Kim
    • 10
  1. 1.Department of RadiologyInje University Pusan Paik HospitalPusanKorea
  2. 2.Division of Pediatric OrthopaedicsSeoul National University Children’s HospitalSeoulKorea
  3. 3.Department of Laboratory MedicineSeoul National University Bundang HospitalKyunggiKorea
  4. 4.Department of GeneticsSouthern California Permanente Medical GroupLos AngelesUSA
  5. 5.Department of PediatricsInje University Pusan Paik HospitalPusanKorea
  6. 6.Department of Orthopaedic SurgeryInje University Haeundae Paik HospitalPusanKorea
  7. 7.Department of RadiologyPusan National University HospitalPusanKorea
  8. 8.Medical Genetics InstituteCedars-Sinai Medical CenterLos AngelesUSA
  9. 9.Department of PediatricsUniversity of LausanneLausanneSwitzerland
  10. 10.Department of RadiologyAjou University HospitalYoungtong-guRepublic of Korea

Personalised recommendations