Cardiac Hypertrophy, Heart Failure and Cardiomyopathy
Mary N. Sheppard in Practical Cardiovascular Pathology, 2022
Danon disease, a glycogen storage disorder, is a rare X-linked dominant disease due to primary deficiency of LAMP2. Excess glycogen accumulates in cardiomyocytes and skeletal muscle fibres leading to formation of vacuoles that stain positive with periodic acid Schiff (Fig. 5.47). Typically affected adolescent males present with the triad of HF, predominantly a HCM phenotype with extreme hypertrophy and LV wall thickness of up to 60 mm, skeletal myopathy and mental retardation. Wolff-Parkinson-White syndrome occurs in both men and women. Skeletal muscle or cardiac biopsy demonstrate vacuolization, immunohistochemistry shows LAMP2 protein deficiency, and sequencing of the LAMP2 gene for mutations is diagnostic. Clinical deterioration with rapidly progressive HF or sudden death before the age of 25 years is characteristic of the disease. No disease specific therapy is available.
Metabolic Myopathy
Maher Kurdi in Neuromuscular Pathology Made Easy, 2021
One of the common differential diagnoses of Pompe disease is Danon disease, type-III GSD and GSD-V. Danon disease is an x-linked pattern characterized by subsarcolemmal vacuolations of glycogen droplets but with normal acid maltase enzyme and no acid phosphatase activity in the vacuoles. Labeling of lectin in the vacuoles was shown in Danon disease but not in Pompe disease.
Neuropsychological functioning following cardiac transplant in Danon disease
Published in Developmental Neurorehabilitation, 2019
David Salisbury, Katherine Meredith
Danon disease is a rare X-linked genetic disorder resulting from lysosome-associated membrane protein 2 (LAMP2) mutation, which leads to glycogen accumulation primarily in cardiac and skeletal muscles.1–3 Both females and males may be affected; however, males appear to experience an earlier onset and more severe symptomatology resulting in cardiac transplant and/or death in the first three decades of life.2 While the prevalence of Danon disease is unclear, studies have reported this disease is present in 1 in 25 pediatric patients presenting with hypertrophic cardiomyopathy and 1 in 6 patients presenting with left ventricular wall thickening and electrocardiogram findings including pre-excitation.1 The disorder is further characterized by a triad of symptoms including skeletal myopathy, cardiomyopathy, and intellectual disability with the latter most pronounced in males.1–4
Danon disease presenting with early onset of hypertrophic cardiomyopathy and peripheral pigmentary retinal dystrophy in a female with a de novo novel mosaic mutation in the LAMP2 gene
Published in Ophthalmic Genetics, 2019
Monika Meinert, Elisabet Englund, Carola Hedberg-Oldfors, Anders Oldfors, Björn Kornhall, Catarina Lundin, Elisabeth Wittström
Danon disease is a rare, serious cardiac and neuromuscular disorder. The exact prevalence is unknown, and the majority of physicians and most ophthalmologists are unfamiliar with the disease. Danon disease is an X-linked, dominant disorder characterized by progressive cardiomyopathy, muscle weakness, and mild intellectual disability, together with retinal, hepatic and pulmonary disorder. The disease is associated with lysosomal defects due to a mutation of the lysosome-associated membrane protein2 (LAMP2) gene (1). The accumulation of autophagic material, and often glycogen, within vacuoles in various tissues is seen in patients with primary LAMP2 protein deficiency secondary to various mutations in the LAMP2 gene, leading to systemic pathology (1,2).
Recommendations and guidance on the diagnosis and management of Danon disease
Published in Expert Opinion on Orphan Drugs, 2021
Kimberly N. Hong, Michela Brambatti, Sonya John, Quan M. Bui, Marzia Rigolli, Matthew Taylor, Eric D. Adler
Danon disease is a multisystemic disorder characterized by the classical triad of severe cardiomyopathy, skeletal myopathy and cognitive impairment, but can include retinopathy as well as gastrointestinal, hepatic and pulmonary manifestations (Table 1). Hepatic and pulmonary symptoms are often sequelae of progressive cardiac and skeletal muscle disease. Notably, while mild cognitive and muscular impairments may have been present since childhood, the cardiovascular symptoms are typically the first symptoms that trigger diagnostic work-ups. Thus, at the time of diagnosis, simultaneous reporting of all these symptoms is common [16,17].
Related Knowledge Centers
- Cardiomyopathy
- Genetic Testing
- Retina
- Hypertrophic Cardiomyopathy
- Lysosome
- Wolff–Parkinson–White Syndrome
- Glycogen Storage Disease Type II
- Gene
- Lamp2
- Glycogen Storage Disease