Multi-disciplinary team of the treatment of heart transplantation for Danon disease / 器官移植

Objective To improve the understanding of Danon disease and the efficacy of heart transplantation by multi-disciplinary team (MDT) pattern. Methods Prior to heart transplantation, MDT consultation was performed on one case of Danon disease, an extremely rare X-chromosome dominant genetic disease. The content of consultation included surgical indication, preoperative preparation and postoperative precaution, as well as the role of MDT in the treatment of Danon disease was summarized. Results Preoperative echocardiography showed that the patient presented withdilated-phase of hypertrophic cardiomyopathy complicated with heart failure, which was considered as Danon disease with end-stage heart failure. After MDT consultation, the patient received the preoperative treatment including anti-heart failure, reduction of pulmonary artery pressure, intra-aortic balloon pump (IABP) assistance, liver protection, strengthening nutritional support, etc. The patient underwent orthotopic heart transplantation after a suitable donor was matched. The patient developed muscle weakness in the limbs 5 days after operation, which was gradually mitigated after reducing the dose of glucocorticoid. At postoperative 48 days, the patient was discharged in good condition and continually treated with triple immunosuppressive regimen after discharge. Reexamination at postoperative 6 months revealed that the patient was in good health without any abnormality in electrocardiogram and echocardiography images. Conclusions Danon disease is extremely rare and MDT pattern may enhance the efficacy and safety of treatment by heart transplantation.

Identification of LAMP2 mutations in early-onset hypertrophic cardiomyopathy by targeted exome sequencing

X-linked dominant mutations in lysosome-associated membrane protein 2 (LAMP2) gene have been shown to be the cause of Danon disease, which is a rare disease associated with clinical triad of cardiomyopathy, skeletal myopathy, and mental retardation. Cardiac involvement is a common manifestation and is the leading cause of death in Danon disease. We report a case of a 24-month-old boy with hemizygous LAMP2 mutation who presented with failure to thrive and early-onset hypertrophic cardiomyopathy. We applied targeted exome sequencing and found a novel hemizygous c.692del variant in exon 5 of the LAMP2 gene, resulting a frameshift mutation p.Thr231Ilefs*11. Our study indicates that target next-generation sequencing can be used as a fast and highly sensitive screening method for inherited cardiomyopathy.

Cystoid macular edema in a patient with Danon disease.

To report a patient with Danon retinopathy with cystoid macular edema treated with topical dorzolamide 2% eye drops and oral acetazolamide. A 37-year-old Caucasian man with Danon disease treated with topical and oral carbonic anhydrase inhibitors participated in the study. Examinations performed before and during treatment included visual acuity (VA), spectral-domain optical coherence tomography, and electroretinography. Following total 48 weeks of treatment, VA decreased from 20/30 OD, 20/200 OS, to 20/40 OD, CF OS. The mean central retinal thickness was unchanged from baseline 263 μm OD , 226 μm OS, after treatment 283 μm OD and 202 μm OS. In our case, carbonic anydrase inhibitors were not effective. However, a general recommendation cannot be given based on a single case.

A Case of Suspected Danon Disease Presenting as a Hypertrophic Cardiomyopathy

Danon disease is characterized clinically by the triad of cardiomyopathy, myopathy and mental retardation. It was originally reported as a lysosomal glycogen storage disease with normal acid maltase by Danon. Danon disease results from mutations in lysosome associated membrane protein-2 (LAMP-2) gene. The LAMP-2 gene is located on Xq24-25. We report a case of suspected Danon disease in patient who had hypertrophic cardiomyopathy and mental retardation along with abnormal findings in electromyography.