The late diagnosis of Danon disease: the morphological characteristics of LAMP2-cardiomyopathy (case report)

Danons disease is a rare and difficult-to-diagnose X-linked hereditary disease caused by a deficiency of lysosome-associated membrane protein 2 or LAMP2. The main clinical symptoms include myocardial damage with the development of hypertrophic LAMP2 cardiomyopathy, skeletal myopathy, and intellectual impairment. The disease is characterized by a rapidly progressive course, which requires dynamic monitoring of patients. The most significant adverse prognostic factor and the main cause of death is the development of cardiomyopathy. But lysosomal accumulation of glycogen in cardiomyocytes often remains unrecognized as the cause of hypertrophic cardiomyopathy. The aim of the study was to conduct a clinical and morphological analysis of a case of late diagnosis of LAMP2 cardiomyopathy in a 44-year-old female patient. We used data from the medical history, the results of intravital laboratory and instrumental studies, qualitative and quantitative morphological studies of endomyocardial biopsy. The results of the study present clinical signs, the results of a morphological study at the light-optical and electronic microscopic levels, and show the features of the structural rearrangement of cardiomyocytes. The formation of multilamellar myelin-like structures under the sarcolemma of cardiomyocytes was found. There were signs of cell damage - significant uneven vacuolization of the sarcoplasm with the detection of fragments of PAS-positive content in individual vacuoles, distortion of cardiomyocytes. There was a disappearance of transverse striation and local violations of the integrity of the sarcolemma. The interstitium was characterized by loose lymphomononuclear infiltration with an admixture of single segmented leukocytes, edema, and small-focal sclerosis, predominantly of the perimuscular type. In the elements of the microvasculature at the light-optical level, signs of endothelial activation were observed. Based on the combination of clinical and anamnestic data, the results of molecular genetic, morphological studies, a metabolic cause of myocardial hypertrophy, previously not clinically recognized, was established with a morphological picture of LAMP2 cardiomyopathy - Danon disease, and an appropriate diagnosis was made. The authors present a rare case of late detection of Danon disease (LAMP2-cardiomyopathy) with the accumulation of autophagocytic material, glycogen in the sarcoplasm of cardiomyocytes, and the formation of osmiophilic myelin-like structures. The presented clinical case clearly demonstrates the practical significance of ultrastructural pathological examination of endomyocardial biopsy to determine the true form of metabolic hypertrophy and assess the degree of morphological myocardial rearrangement.