Danon Disease: Entire LAMP2 Gene Deletion with Unusual Clinical Presentation-Case Report and Review of the Literature.

Danon disease is a rare x-linked dominant multisystemic disorder with a clinical triad of severe cardiomyopathy, skeletal myopathy, and intellectual disability. It is caused by defects in the lysosome-associated membrane protein-2 (LAMP2) gene. Numerous different mutations in the LAMP2 protein have been described. Danon disease is typically lethal by the mid-twenties in male patients due to cardiomyopathy and heart failure. Female patients usually present with milder and variable symptoms. This report describes a 42-year-old father and his 3-year-old daughter presenting with mild manifestations of the disease. The father has normal intellectual development and normal physical activity. At the age of 13, he was diagnosed with mild ventricular pre-excitation known as Wolf-Parkinson-White syndrome (WPWs), very mild and mostly asymptomatic cardiomyopathy and left ventricular hypertrophy, and at about the age of 25 presented with visual impairment due to cone-rod dystrophy. His daughter showed normal development and very mild asymptomatic electrocardiographic WPWs abnormalities with left mild ventricular hypertrophy. Genetic testing revealed an Xq24 microdeletion encompassing the entire LAMP2 gene. Relevant literature was reviewed as a reference for the etiology, diagnosis, treatment and case management.

The impact of left ventricular ejection fraction on heart failure patients with pulmonary hypertension.

BACKGROUND: The most common cause of pulmonary hypertension (PH) in developed countries is left heart disease (LHD, group 2 PH). The development of PH in heart failure (HF) patients is indicative of worse outcomes. OBJECTIVE: The aim of this study was to evaluate the long term outcomes of HF patients with PH in a national long-term registry. METHODS: Study included 9 cardiology centers across Israel between 01/2013-01/2015, with a 12-month clinical follow-up and 24-month mortality follow-up. Patients were age ≥18 years old with HF and pre-inclusion PH due to left heart disease determined by echocardiography [estimated systolic pulmonary arterial pressure (SPAP) ≥ 50 mmHg]. Patients were categorized into 3 groups: HF with reduced (HFrEF < 40%), mid-range (HFmrEF 40-49%), and preserved (HFpEF ≥ 50%) ejection fraction. RESULTS: The registry included 372 patients, with high prevalence of cardiovascular risk factors. Median HF duration was 4 years and 65% were in severe HF New York Heart Association (NYHA) classification ≥3. Mean systolic pulmonary artery pressure (SPAP) was 62 ± 11 mmHg. During 2-years of follow-up, 54 patients (15%) died. Univariable predictors of mortality included NYHA grade 3-4, chronic renal failure, and SPAP ≥ 65 mmHg. Severe PH was associated with mortality in HFpEF, but not HFmrEF or HFrEF, and remained significant after multivariable adjustment with an adjusted hazard ratio of 2.99, (95%CI 1.29-6.91, p = 0.010). CONCLUSIONS: The combination of HFpEF with severe PH was independently associated with increased mortality. Currently, HFpEF patients are included with group 2 PH patients. Defining HFpEF with severe PH as a sub-class may be more appropriate, as these patients are at increased risk and deserve special consideration.