Danon disease: a case report and literature review

Abstract

Background Danon disease (DD) is a rare x-linked dominant multisystemic disorder with a clinical triad of severe cardiomyopathy, skeletal myopathy, and mental retardation. It is caused by a defect in the lysosomal-associated membrane protein-2 (LAMP2) gene, which leads to the formation of autophagic vacuoles containing glycogen granule deposits in skeletal and cardiac muscle fibers. So far, more than 50 different mutations in LAMP2 have been identified. Case presentation Here, we report an 18-year-old male patient who was hospitalized for heart failure. Biopsy of the left lateral femoral muscle revealed scattered autophagic vacuoles in the muscle fibers with increased glycogen. Next generation sequencing (NGS) was used to detect gene mutations of the proband sample and a novel frameshift mutation (c.1052delG) has been identified in exon 8 of LAMP2, which leads to truncation of the protein. Conclusion We found a novel frameshift mutation, a hemizygous mutation (c.1052delG) in exon 8 of LAMP2, identified as presenting the hypertrophic cardiomyopathy (HCM) phenotype. Genetic analysis is the gold standard for the diagnosis of DD and is essential to determine appropriate treatment strategies and to confirm the genetic risk of family members.

De novo LAMP2 insertion mutation causes cardiac-only Danon disease: A case report

“…HE staining of the section revealed unstructured cardiac cells (Figure 3A). PAS staining showed small vacuoles and glycogen disposition within cardiac muscle fibers (Figure 3B), which was similar to previously reported pathological features of the Danon disease (2). IHC staining of the heart tissue showed high and low expressing patches of LAMP2 (Figure 4C).…”

“…Danon disease (OMIM: 300257) is an X-linked dominant disorder caused by a defect of the lysosome-associated membrane protein 2 (LAMP2) gene (1). LAMP2 is essential in the progress of the autophagosome maturation (2). Mutations of LAMP2 identified in Danon disease lead to splicing defects or protein truncation, which underlies LAPM2 deficiency in skeletal and cardiac muscles (1).…”

“…In male patients, cardiac symptoms usually began in infancy/childhood or adolescence, while females present with slower progression and later onset of the disease. In some female patients, the cardiac disease may act as an isolated clinical feature (73%) (2).…”

Hypertrophic cardiomyopathy secondary to deficiency in lysosome-associated membrane protein-2: A case report

“…Young male patients with DD typically present with left ventricular hypertrophy, which, unfortunately, is frequently mistaken for hypertrophic cardiomyopathy or other secondary conditions related to left ventricular hypertrophy. Characterized by rapid progression and a propensity for high mortality at an early age, DD may be the most lethal cardiomyopathy in young male patients[ 3 ]. In the present case study, we describe the patient’s clinical course from hospital admission to death, including all diagnostic work-ups, his treatment course, and any notable noninvasive imaging features.…”

Dilated Cardiomyopathy and Systolic Heart Failure in a Female Patient With Danon Disease

“…Danon disease is a rare multisystem X-linked dominant disorder associated with a defect in the lysosomal-associated membrane protein-2 (LAMP2) gene [ 1 ]. The clinical triad of Danon disease includes skeletal myopathy, intellectual disability, and hypertrophic cardiomyopathy with male patients presenting earlier and with a more severe phenotype than female patients [ 2 ]. Female patients typically present with isolated hypertrophic cardiomyopathy which accounts for the majority of known female phenotypes [ 1 , 3 , 4 ].…”