Journal of Inherited Metabolic Disease

, Volume 34, Issue 2, pp 515–522

Danon disease: intrafamilial phenotypic variability related to a novel LAMP-2 mutation

  • Sarah-Louise Cottinet
  • Anne-Marie Bergemer-Fouquet
  • Annick Toutain
  • Frédérique Sabourdy
  • Zoha Maakaroun-Vermesse
  • Thierry Levade
  • Alain Chantepie
  • François Labarthe
Original Article

DOI: 10.1007/s10545-010-9251-y

Cite this article as:
Cottinet, SL., Bergemer-Fouquet, AM., Toutain, A. et al. J Inherit Metab Dis (2011) 34: 515. doi:10.1007/s10545-010-9251-y

Abstract

Danon disease is an X-linked lysosomal disorder, characterized by hypertrophic cardiomyopathy, skeletal myopathy and mental retardation. We report a family with a novel mutation, in which the mother and her three sons were affected with various clinical presentations. A massive hypertrophy of the left ventricle was the predominant feature in the three male patients, with different degrees of severity of cardiac symptoms, from isolated palpitations to cardiac failure and sudden death. Muscle pain and weakness were also variable, but constantly associated with increased plasma CK levels. Finally, the male patients had variable degree of a mental retardation. The mother had an attenuated phenotype, limited to a mild hypertrophic cardiomyopathy with premature ventricular contractions diagnosed during her 40’s. Microscopy examination of skeletal muscle biopsy, performed in the youngest patient, demonstrated atrophic myofibers with intracytoplasmic vacuoles suggesting lysosomal glycogen storage disease. Immunohistochemistry analyses in muscle specimen showed no detectable Lysosomal-Associated Membrane Protein-2 (LAMP-2), in keeping with the diagnosis of Danon disease. However, a very low expression of a shortened LAMP-2 protein could be evidenced by Western-blot in the patient’s fibroblasts. Molecular investigations identified a novel splicing mutation (IVS6 + 1delG) in the LAMP-2 gene. This case report highlights the intrafamilial variability of Danon disease phenotype. In this case, morphological examination of muscle biopsy, showing lysosomal storage myopathy, and immunohistochemistry analyses can provide key elements for orienting etiologic investigations.

Abbreviations

BNP

B-type natriuretic peptide

CK

Creatine kinase

HES

Hematoxylin and eosin staining

LAMP

Lysosomal-associated membrane protein

PAS

Periodic acid schiff staining

Copyright information

© SSIEM and Springer 2010

Authors and Affiliations

  • Sarah-Louise Cottinet
    • 1
  • Anne-Marie Bergemer-Fouquet
    • 2
  • Annick Toutain
    • 3
  • Frédérique Sabourdy
    • 4
    • 5
  • Zoha Maakaroun-Vermesse
    • 1
  • Thierry Levade
    • 4
    • 5
  • Alain Chantepie
    • 1
  • François Labarthe
    • 1
    • 6
    • 7
  1. 1.Service de Médecine Pédiatrique, CHRU de ToursUniversité François RabelaisToursFrance
  2. 2.Service d’anatomie et cytologie pathologiques, CHRU de ToursUniversité François RabelaisToursFrance
  3. 3.Service de Génétique, CHRU de ToursUniversité François RabelaisToursFrance
  4. 4.Laboratoire de Biochimie Métabolique, Institut Fédératif de Biologie, CHU ToulouseToulouseFrance
  5. 5.INSERM U858, I2MRToulouseFrance
  6. 6.INSERM U921ToursFrance
  7. 7.Service de Médecine PédiatriqueHôpital Clocheville, CHRU ToursToursFrance

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