Psychiatric and cognitive characteristics of individuals with Danon disease (LAMP2 gene mutation).

Danon disease (DD) is a rare X-linked disorder caused by loss-of-function mutations in the LAMP2 gene, which encodes lysosome-associated membrane protein. It is characterized by the triad of hypertrophic cardiomyopathy, myopathy, and intellectual disability. Whereas the molecular and pathophysiological mechanisms underlying this disorder have been previously reported and continue to be explored, the cognitive deficits and psychiatric comorbidities manifested in DD remain an understudied topic. We systematically assessed cognitive abilities and psychiatric comorbidities in 13 males and females. Most of the participants in our cohort (n = 9; 75%) had an IQ score within the normal range, while only one participant had intellectual disability. Participants' performance on the Cognitive Neuropsychiatric Battery (CNB) showed only mildly impaired cognitive abilities in most modules, except in the executive functioning test, which was low compared to healthy controls. Of note, 69% of the participants met criteria for at least one psychiatric disorder, mainly mood and anxiety disorders, occurring alone or in combination in the same patient. The results of the present study challenge earlier reports suggesting that mental retardation is a core constituent in DD. Of importance, it underscores the need to refer Danon patients to psychiatric assessment.

Efficacy of exercise training in symptomatic patients with hypertrophic cardiomyopathy: results of a structured exercise training program in a cardiac rehabilitation center.

BACKGROUND: Recent data suggest that exercise training (ET) confers significant symptomatic and functional improvements in patients with diastolic dysfunction, and thus may be beneficial in patients with hypertrophic cardiomyopathy (HCM). However, there are no data regarding the safety or efficacy of ET in HCM patients. DESIGN: A prospective non-randomized intervention design was used. METHODS: We enrolled 20 patients with symptomatic HCM, significantly limited in everyday activity, into a supervised cardiac rehabilitation exercise program. RESULTS: Patients were 62 ± 13 years old, in New York Heart Association (NYHA) functional class II (35%) or III (65%), had a mean interventricular septum dimension of 17 ± 5 mm and left ventricular ejection fraction (LVEF) of 53 ± 15%. Left ventricular outflow gradient was present at rest in nine patients (mean 51 ± 24 mm Hg) and six patients had an implantable defibrillator. Exercise prescription was based on heart rate reserve (HRR) determined from a symptom-limited graded exercise stress test. Exercise intensity was gradually increased from 50% to 85% of the HRR over the training period. Patients completed an average of 41 ± 8 hours of aerobic ET. No adverse events or sustained ventricular arrhythmias occurred during the training program. Functional capacity, assessed by a graded exercise test, improved from 4.7 ± 2.2 to 7.2 ± 2.8 metabolic equivalents (METs) (p = 0.01). NYHA functional class improved from baseline by ≥ 1 grade in 10 patients (50%) and none experiencing deterioration during follow-up. CONCLUSIONS: The present study suggests that patients with HCM who remain symptomatic despite medical therapy may achieve considerable functional improvement through a supervised ET program.