title: Early onset of cardiomyopathy and intellectual disability in a girl with Danon disease associated with a de novo novel mutation of the LAMP2 gene.
abstract: Danon disease, primary lysosome-associated membrane protein-2 (LAMP-2) deficiency, is characterized clinically by cardiomyopathy, myopathy and intellectual disability in boys. Because Danon disease is inherited in an X-linked dominant fashion, males are more severely affected than females, who usually have only cardiomyopathy without myopathy or intellectual disability; moreover, the onset of symptoms in females is usually in adulthood. We describe a girl with Danon disease who presented with hypertrophic cardiomyopathy and Wolff-Parkinson-White (WPW) syndrome at 12 years of age. Subsequently, she showed signs of mild learning disability and intellectual disability on psychological examinations. She had a de novo novel mutation in the LAMP-2 gene and harbored an identical c.749C > A (p.Ser250X) variant, resulting in a stop codon in exon 6. She showed decreased, but not completely absent LAMP-2 expression on immunohistochemical and Western blot analyses of a skeletal muscle biopsy specimen, which has been suggested to be caused by a 50% reduction in LAMP-2 expression (LAMP-2 haploinsufficiency) in female patients with Danon disease caused by a heterozygous null mutation. To our knowledge, our patient is one of the youngest female patients to have been given a diagnosis of Danon disease. In addition, this is the first documented case in a girl that was clearly associated with intellectual disability, which is very rare in females with Danon disease. Our findings suggest that studies of female patients with Danon disease can extend our understanding of the clinical features of this rare disease.
authors.affiliation: Department of Neurology, Nara Medical University School of Medicine, Kashihara, Nara, Japan.|Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), Kodaira, Tokyo, Japan.
authors.forename: Kazuma
authors.initials: K
authors.lastname: Sugie
authors.affiliation: Department of Pediatrics, Nara Medical University School of Medicine, Kashihara, Nara, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yoshizawa
authors.affiliation: First Department of Internal Medicine, Nara Medical University School of Medicine, Kashihara, Nara, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Onoue
authors.affiliation: Department of Psychiatry, Nara Medical University School of Medicine, Kashihara, Nara, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Nakanishi
authors.affiliation: Department of Neurology, Nara Medical University School of Medicine, Kashihara, Nara, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Eura
authors.affiliation: Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), Kodaira, Tokyo, Japan.
authors.forename: Megumu
authors.initials: M
authors.lastname: Ogawa
authors.affiliation: First Department of Internal Medicine, Nara Medical University School of Medicine, Kashihara, Nara, Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Nakano
authors.affiliation: First Department of Internal Medicine, Nara Medical University School of Medicine, Kashihara, Nara, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Sakaguchi
authors.affiliation: Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), Kodaira, Tokyo, Japan.
authors.forename: Yukiko K
authors.initials: YK
authors.lastname: Hayashi
authors.affiliation: Department of Psychiatry, Nara Medical University School of Medicine, Kashihara, Nara, Japan.
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Kishimoto
authors.affiliation: Department of Pediatrics, Nara Medical University School of Medicine, Kashihara, Nara, Japan.
authors.forename: Midori
authors.initials: M
authors.lastname: Shima
authors.affiliation: First Department of Internal Medicine, Nara Medical University School of Medicine, Kashihara, Nara, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Saito
authors.affiliation: Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), Kodaira, Tokyo, Japan.
authors.forename: Ichizo
authors.initials: I
authors.lastname: Nishino
authors.affiliation: Department of Neurology, Nara Medical University School of Medicine, Kashihara, Nara, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ueno
mesh_terms: D000293:Adolescent; D009202:Cardiomyopathies / Q000209:etiology*; D005260:Female; D052120:Glycogen Storage Disease Type IIb / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000523:psychology; D006801:Humans; D008607:Intellectual Disability / Q000209:etiology*; D052119:Lysosomal-Associated Membrane Protein 2 / Q000235:genetics*; D018482:Muscle, Skeletal / Q000473:pathology; D009154:Mutation; D014927:Wolff-Parkinson-White Syndrome / Q000150:complications
chemical_list: C497811:LAMP2 protein, human; D052119:Lysosomal-Associated Membrane Protein 2
keywords: Danon disease; autophagic vacuoles; cardiomyopathy; intellectual disability; lysosome-associated membrane protein-2 (LAMP-2)