Anti-LAMP2 monoclonal antibody, clone M3/84 [R-PE]

Danon disease is a neuromuscular disorder with variable expression in the eye. We describe a family with Danon disease and cone-rod dystrophy (CRD). Affected males of one family with Danon were invited for an extensive ophthalmologic examination, including color vision testing, fundus photography, Goldmann perimetry, full-field electroretinogram (ERG), and SD-OCT. Previous ophthalmologic data were retrieved from medical charts. The LAMP2 and RPGR gene were analyzed by direct sequencing. Two siblings had no ocular phenotype. The third sibling and a cousin developed CRD leading to legal blindness. Visual acuity deteriorated progressively over time, color vision was severely disturbed, and ERG showed reduced photopic and scotopic responses. SD-OCT revealed thinning of the photoreceptor and RPE layer. Visual fields demonstrated central scotoma. The causal mutation was p.Gly384Arg in LAMP2; no mutations were found in RPGR. This is the first description of CRD in Danon disease. The retinal phenotype was a late onset but severe dystrophy characterized by loss of photoreceptors and RPE cells. With this report, we highlight the importance of a comprehensive ophthalmologic examination in the clinical work-up of Danon disease.

Danon disease is caused by mutations of the lysosome-associated membrane protein-2 (LAMP2) gene at Xq24. Male patients usually manifested as severe cardiomyopathy, mild myopathy and mental retardation. We describe two patients: the first patient presented with severe hypertrophic cardiomyopathy, Wolff-Parkinson-White syndrome, proximal muscle weakness, and chronic painless diarrhea; the second patient manifested as limb-girdle muscle weakness, mild left ventricular diastolic dysfunction, sub-clinical neuropathy. Muscle biopsies indicated autophagic vacuolar myopathy. Immunologic analysis demonstrated absence of the LAMP2 protein in the first patient, while a smear of expression was detected in the second patient. Two nonsense mutations (p.E298X and p. K402X) were identified in the two cases, respectively located in exon 7 and exon 9B of the LAMP2 gene. Our findings indicated that patients with Danon disease caused by mutations in exon 1 - 8 manifested as a typically severe phenotype, while patients with mutations in exon 9 of the LAMP2B isoform presented with a relatively benign phenotype.