Clinical and genetic profile of Chinese children with Danon disease: A single-center retrospective cohort study.

Background: Danon disease (DD) is a rare X-linked dominant lysosomal storage disorder. Studies on DD pediatric patients are limited due to the small number of cases and challenges in early detection.

Methods: We retrospectively analyzed clinical and genetic data of 29 pediatric patients who visited our hospital for treatment or genetic counseling of DD from July 2014 to December 2023.

Results: The mean age at diagnosis was 7.2±5.9 years for males (n=21) and 9.4±5.0 years for females (n=8). Asymptomatic elevated liver aminotransferase and/or creatine kinase (CK) levels were initial manifestations detected in 10 (48%) male patients and absent in female patients. Hypertrophic cardiomyopathy (HCM) was observed in 20 (95%) male and 7 (88%) female patients, while dilated cardiomyopathy (DCM) was not detected. Ventricular preexcitation (VP) was observed initially in 10 (36%) patients and in 15 (54%) at latest evaluation. Patients with VP had higher left ventricular posterior wall thickness in diastole z-scores than those without VP (5.6±2.2 vs. 3.5±2.1, p=0.029). During a median 2.7-years follow-up, two males received heart transplants. One boy and one girl died of heart failure and sudden cardiac arrest, respectively. Twenty-three pathogenic LAMP2 variants were identified, including seven novel variants.

Conclusions: A retrospective review of 29 DD cases suggests an underrecognized asymptomatic period in male DD patients, characterized by elevations in serum CK and transaminases. HCM appears to be the only cardiac manifestation in pediatric female patients, unlike a high incidence of DCM in adult female patients. The incidence of VP may increase with disease progression.