Clinical and Genetic Profile of Chinese Children With Danon Disease: A Single-Center Retrospective Cohort Study.

Abstract

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

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

Results: The mean age at diagnosis was 7.2 ± 5.9 years for boys (n = 21) and 9.4 ± 5.0 years for girls (n = 8). Asymptomatic elevated liver transaminase or creatine kinase (CK) levels were initial manifestations detected in 10 male patients (48%) and absent in female patients. Hypertrophic cardiomyopathy (HCM) was observed in 20 male patients (95%) and 7 female patients (88%), whereas dilated cardiomyopathy (DCM) was not detected. Ventricular preexcitation (VP) was observed initially in 10 patients (36%) and in 15 (54%) at latest evaluation. Patients with VP had higher left ventricular posterior wall thickness in end-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 of follow-up, 2 male patients received heart transplants. One boy and 1 girl died of heart failure and sudden cardiac arrest, respectively. Twenty-three pathogenic LAMP2 variants were identified, including 7 novel variants.

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