Danon disease with typical early‐onset cardiomyopathy in a male: Focus on a novel LAMP‐2 mutation

Abstract

We report a case of a 16-yr-old male with Danon disease caused by a novel mutation in the LAMP-2 gene. Mutations in the LAMP-2 gene result in the absence of LAMP-2 on immunohistochemical staining of muscle tissue, thus defining Danon disease, a rare X-linked myopathy. It is characterized clinically by HCM or left ventricular hypertrophy, a WPW pattern on ECG, variable degrees of muscular weakness (skeletal myopathy), mental retardation, and retinal changes. The patient presented with severe skeletal muscular weakness and respiratory failure. He also had a history of two OHTs, the first one for severe HCM and the second for allograft rejection. The patient's myopathy was initially presumed to be exclusively related to steroid-induced "critical care myopathy." However, further evaluation with a thigh muscle biopsy revealed autophagic vacuoles with sarcolemnal features suggestive of a lysosomal storage disorder. DNA analysis ultimately identified a previously unreported hemizygous IVS6+3_+6delGAGT splice site deletion mutation in the LAMP-2 gene located within the 5' splice site of intron 6, consistent with Danon disease.

Origin and development of the atrioventricular myocardial lineage: Insight into the development of accessory pathways

“…Several genes have been associated with the formation of accessory pathways in familial preexcitation, including LAMP2 (encoding lysosome-associated membrane glycoprotein 2) and PRKAG2 (encoding regulatory gamma 2 -subunit of the AMP-activated protein kinase; Bui et al, 2008;Yang et al, 2010). Mutations in LAMP2 or PRKAG2 cause a hypertrophic cardiomyopathy like phenotype due to defective glycogen storage, which is distinguished by electrophysiological abnormalities, particularly ventricular preexcitation.…”

Defective Tbx2-dependent patterning of the atrioventricular canal myocardium causes accessory pathway formation in mice

“…Mutations in LAMP2 (50,51) and PRKAG2 (35,52) are linked to the formation of accessory pathways. In these glycogen storage diseases, it has been proposed that glycogen toxicity causes annulus fibrosus thinning that underlies formation of accessory pathways (35,52).…”

Review: Danon disease: Review of natural history and recent advances

“…The majority of patients progressed rapidly to heart failure with end‐stage LV dysfunction , and HTx being the best chance for long‐term survival . Although the first HTx in DD was reported in 1994 , it has only been performed in 5–33% of patients so far .…”

“…The long‐term follow‐up of two patients who underwent HTx showed that they were in good clinical condition at age 46 years (21 years after HTx) and at age 43 years (9 years after HTx) respectively . Three patients required retransplant due to allograft rejection . Some patients developed profound muscle weakness after HTx, which resolved with steroid withdrawal .…”