Clinical features of pediatric Danon disease and the importance of early diagnosis.

ABSTRACT

Successful therapy in a cohort with early onset Danon disease (DD) highlights the potential importance of earlier disease recognition. We present experience from the largest National Pediatric Center in Russia for cardiomyopathy patients. This report focuses on identification of early clinical features of DD in the pediatric population by detailed pedigree analysis and review of medical records. RESULTS: Nine patients (3 females) were identified with DD at the Russian National Medical Research Center of Children's Health ("National Pediatric Center") aged birth to 16 years. At presentation/evaluation all patients had left ventricular hypertrophy (LVH), ECG features of Wolff-Parkinson-White (WPW), and an increase in hepatic enzymes (particularly lactate dehydrogenase (LDH)); three had marked increase in NT-proBNP; two had HCM with impaired LV function; one had LVH with LV noncompaction; five had arrhythmia with paroxysmal supraventricular and/or ventricular tachycardia. Two teenagers died at ages 16-17 from refractory heart failure and two underwent heart transplantation. All patients were found to have a pathogenic/likely pathogenic variant in the LAMP2 gene, six patients had no family history and a de novo evolvement was documented in 4/6 of those available for genetic tested. Retrospective review related to family background and earlier clinical evaluations revealed a definitive or highly suspicious family history of DD in 3, early clinical presentation with cardiac abnormalities (ECG, echo) in 3, and cerebral, hepatic and/or neuromuscular symptoms in 5. Abnormalities were detected 9,5 months to 5,8 years, median 3,5 years prior to referral to the National Pediatric Center. CONCLUSION: The earliest clinical manifestations of Danon disease occur in the first 12 years of life with symptoms of skeletal muscle and cerebral disease, raised hepatic enzymes, and evidence of cardiac disease on ECG/echo.