Phenotypic heterogeneity in two unrelated danon patients associated with the same LAMP-2 gene mutation

E. Bertini, M. A. Donati, P. Broda, D. Cassandrini, S. Petrini, C. Dionisi-Vici, L. Ballerini, R. Boldrini, A. D'Amico, E. Pasquini, C. Minetti, F. M. Santorelli, C. Bruno

Research output: Contribution to journalArticle

Abstract

Danon disease, an X-linked cardioskeletal myopathy caused by primary deficiency of lysosome-associated membrane protein-2 (LAMP-2), is clinically characterized by cardiomyopathy, myopathy, and variable mental retardation. The pathological hallmark of the disease is the absence of LAMP-2 immunohistochemical staining in muscle. The LAMP-2 gene mutations reported thus far are generally private mutations. We describe two cases of Danon disease with different clinical presentation, in whom we identified the same exon skipping mutation c.928G>A in the LAMP-2 gene. The first patient was affected by an early onset myopathy and hypertrophic cardiomyopathy (HCM) that partially improved with drug treatment. A first muscle biopsy at age 4 months showed markedly increased glycogen, and acid maltase deficiency was ruled out biochemically. A second muscle biopsy, performed at age 3 1/2 years, showed very mild abnormalities. The second child at age 15 years had mild, diffuse muscle weakness and wasting, moderate mental deficiency, and HCM. Two serial biopsies performed at age 8 and 15 years showed similar findings of multiple esterase-positive vacuoles in type I myofibers. In both patients the immunohistochemical study demonstrated the absence of LAMP-2 in skeletal muscle.

Original languageEnglish
Pages (from-to)309-313
Number of pages5
JournalNeuropediatrics
Volume36
Issue number5
DOIs
Publication statusPublished - Oct 2005

Keywords

  • Danon disease
  • Hypertrophic cardiomyopathy
  • LAMP-2

ASJC Scopus subject areas

  • Clinical Neurology
  • Pediatrics, Perinatology, and Child Health

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